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Alsalhi A, Spyropoulos F, Batchelor HK. Flexible and dispersible paediatric oral formulations produced via extrusion spheronisation for the treatment of tuberculosis. Int J Pharm 2025; 678:125701. [PMID: 40350000 DOI: 10.1016/j.ijpharm.2025.125701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 05/06/2025] [Accepted: 05/06/2025] [Indexed: 05/14/2025]
Abstract
Until now, there has been a lack of suitable formulations for combined tuberculosis (TB) therapy to treat paediatric populations. The objective of this research was the development and manufacture (at small scale) of an age-appropriate flexible dose combination of dispersible spherical pellets of isoniazid (INH), pyrazinamide (PZD) and rifampicin (RIF) for TB treatment. These pellets were prepared using either crospovidone (XPVP) alone or XPVP in combination with microcrystalline cellulose (MCC) as an extrusion-spheronisation (ES) aid (ES-aid). Each drug was incorporated into ES-aid separately at various APIs/ES-aid proportions: 0:100, 10:90, 40:60, and 60:40, to make spherical pellets using ES. Average Feret diameter (dFer.ave), Raman spectroscopy, texture analysis, disintegration and dissolution testing were used to assess/characterize the formulations produced with a view to enable the production of high-quality pellets with sufficiently high drug loading. Pellets prepared with XPVP alone demonstrated a slightly larger dFer.ave compared to those made with MCC. Although dFer.ave increased as drug loading rose, pellets maintained acceptable sphericity, highlighting the robustness of the formulation process. The most notable distinction between the batches was the rapid disintegration of spheronised pellets containing INH, PZD, RIF, and XPVP within 20-30 s in Simulated Salivary Fluid (SSF) at 37 °C, in contrast to the MCC-based pellets, which remained intact under identical conditions. The dissolution profiles, particularly for RIF and PZD, were significantly faster with XPVP-formulated pellets compared to MCC. These findings aligned with tensile strength data, where XPVP-based pellets, both drug-free and drug-loaded, were less hard than MCC-based pellets, contributing to their superior disintegration and dissolution performance. Age-appropriate flexible dose combination spherical pellets were developed and their properties make them a promising formulation strategy for combination therapy to improve the overall TB treatment in paediatric populations.
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Affiliation(s)
- Alyaa Alsalhi
- School of Pharmacy, Institute of Clinical Sciences, Robert Aitken Building, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Department of Pharmaceutics, Faculty of Pharmacy, King Saud University, Riyadh 11421, Saudi Arabia.
| | - Fotis Spyropoulos
- School of Chemical Engineering, University of Birmingham, Birmingham, West-Midlands B152T, United Kingdom
| | - Hannah K Batchelor
- School of Pharmacy, Institute of Clinical Sciences, Robert Aitken Building, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 04E, United Kingdom.
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A ROS-responsive fluorescent probe detecting experimental colitis by functional polymeric nanoparticles. Int J Pharm 2021; 609:121125. [PMID: 34560209 DOI: 10.1016/j.ijpharm.2021.121125] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/08/2021] [Accepted: 09/19/2021] [Indexed: 12/19/2022]
Abstract
Current evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). TotalROX (λabs/λem = 425/525 nm) is a ratiometric probe with high detection sensitivity and a superior capacity to monitor total cellular oxidative capacity. Herein, we investigated the potential of combining totalROX with an oral nanoparticle delivery system to detect the degree of colitis. This detection system also featured pH-responsive Eudragit S100, hyaluronic acid with high affinity to the CD44 receptor, and chitosan, and demonstrated improved loading efficiency and stability. An experimental mouse model of experimental colitis was induced by dextran sodium sulfate do that we could investigate the ability of our nanoparticles to target the colon and determine the degree of inflammation. We also determined and validated the positive correlation between the fluorescence intensity of the detection product (Ox670, λabs/λem = 650/675 nm) and myeloperoxidase activity (R2 = 0.97) and the histopathological score (R2 = 0.98). TotalROX had significant ability to measure reactive oxygen species (ROS) produced by cells under inflammatory conditions, as confirmed by in vitro experiments with Caco-2 cells. Collectively, the data generated demonstrate that when loaded with totalROX, these functional nanoparticles are promising tools for cellular imaging after oral administration. This is the first description of a ROS-responsive fluorescent probe to evaluate the degree of colitis in experimental animal models and provides a promising approach for the diagnosis of inflammation in IBD with fluorescence-guided colonoscopy.
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Yaghoubi A, Davoodi J, Asgharzadeh F, Rezaie S, Nazari E, Khazaei M, Soleimanpour S. Therapeutic effect of an anti-tuberculosis agent, isoniazid, and its nano-isoform in ulcerative colitis. Int Immunopharmacol 2021; 96:107577. [PMID: 33812254 DOI: 10.1016/j.intimp.2021.107577] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 03/04/2021] [Accepted: 03/08/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Isoniazid (INH) is well known as a first-line anti-tuberculosis, while some studies demonstrate that it has anti-inflammatory activity via a different mechanism such as inhibitionthe production of IL-1, ROS, activation of PPARγ expression, inhibition of the transcriptional regulatory activity of NF-κB and AP-1. The aim of this study, investigate the anti-inflammatory effect of INH and INH combined with Sulfasalazine-loaded nanoparticles (NPs) in the ulcerative colitis mouse model. METHODS To investigate the anti-inflammatory effect of INH and NPs in the ulcerative colitis mice model, we evaluated the effect of INH clinical symptoms and colonic mucosal histology in colitis. RESULT The present study demonstrates that combination therapy of INH with sulfasalazine as well as NPs reduces the symptom of ulcerative colitis and improved disease activity index include body lose weight, diarrhea, rectal bleeding, colonic length, spleen weight, and colon histopathological score in DSS-induced colitis mice model. CONCLUSION Our results suggest that the nanoforms of INH with sulfasalazine enhances the therapeutic effect of the drugs in the treatment of ulcerative colitis.
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Affiliation(s)
- Atieh Yaghoubi
- Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Javid Davoodi
- Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fereshteh Asgharzadeh
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sajad Rezaie
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elnaz Nazari
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Saman Soleimanpour
- Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Aghrbi I, Fülöp V, Jakab G, Kállai-Szabó N, Balogh E, Antal I. Nanosuspension with improved saturated solubility and dissolution rate of cilostazol and effect of solidification on stability. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2020.102165] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Pathania D, Sood S, Saini AK, Kumari S, Agarwal S, Gupta VK. Studies on anticancerious and photocatalytic activity of carboxymethyl cellulose-cl-poly(lactic acid-co-itaconic acid)/ZnO-Ag nanocomposite. ARAB J CHEM 2020. [DOI: 10.1016/j.arabjc.2020.07.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Kaffash E, Saremnejad F, Abbaspour M, Mohajeri SA, Garekani HA, Jafarian AH, Sardo HS, Akhgari A, Nokhodchi A. Statistical optimization of alginate-based oral dosage form of 5-aminosalicylic acid aimed to colonic delivery: In vitro and in vivo evaluation. J Drug Deliv Sci Technol 2019. [DOI: 10.1016/j.jddst.2019.04.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Farooq M, Shoaib MH, Yousuf RI, Qazi F, Hanif M. Development of extended release loxoprofen sodium multiparticulates using different hydrophobic polymers. Polym Bull (Berl) 2018. [DOI: 10.1007/s00289-018-2510-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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Mahkam M. Controlled Release of Biomolecules from pH-Sensitive Hydrogels Prepared by Radiation Polymerization. J BIOACT COMPAT POL 2016. [DOI: 10.1177/0883911504044454] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Copolymers of 2-hydroxyethyl methacrylate and methacrylic acid based hydrogels were studied as hydrogel drug delivery systems. Radiation copolymerization of 2-hydroxyethyl methacrylate and methacrylic acid (mixed with 3,3'-azobis(6-hydroxy benzoic acid)(ABHB) as an azo derivative of 5-aminosalicylic acid were carried out with various amounts of methacryloyloxyethyl esters of terephthalic acid for crosslinking. The polymer structures were characterized by FTIR, 1H NMR, 13C NMR spectroscopy and glass transition temperature (Tg). The hydrolysis of the drug–polymer conjugates were carried out in dialysis bags containing aqueous buffer solutions (pH 1 and 7.4) at 37°C. The drug-release profiles indicate that the amount of drug release depended on the degree of swelling and crosslinking.
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Affiliation(s)
- Mehrdad Mahkam
- Chemistry Department, Faculty of Science, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran
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Mahkam M, Allahverdipoor M, Mohammadi R, Ranaei-Siadat SO, Rashidi MR, Davaran S, Barshan M, Ranaei-Siadat SE. An Oral Delivery System for Insulin. J BIOACT COMPAT POL 2016. [DOI: 10.1177/0883911506063212] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Crosslinked 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) copolymer hydrogels were studied as drug delivery systems. Terephthalic acid was covalently linked with 2-hydroxyethyl methacrylate (HEMA), abbreviated as cross-linking agent (CA). Free radical copolymerization of HEMA and MAA with terephthetalic acid (CA) (2, 4, and 6%) as crosslinking agent were carried out at 70°C. The structure of the CA was confirmed by FT-IR, 1H-NMR and 13C-NMR spectroscopy. The composition of the crosslinked three-dimensional polymers were determined by FTIR spectroscopy. Glass transition temperature (Tg) of the network polymers was determined calorimetrically. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 7.4). The swelling and hydrolytic behavior of the copolymers depended on the content of MAA which caused a decrease in gel swelling in SGF or an increase in gel swelling in SIF. It was observed that in acidic media hydrogen bonds formed due to the protonation of the carboxylic acid groups of the MAA while in more basic or neutral conditions electrostatic repulsion occurred between the ionized carboxylic acid groups. This complex behavior affected the macroscopic swelling properties of the resultant hydrogels. The amount of drug release depended on the degree of hydrogel swelling and crosslinking.
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Affiliation(s)
- M. Mahkam
- Chemistry Department, Azerbaijan University of Tarbiat Moallem, Tabriz, Iran, ,
| | - M. Allahverdipoor
- Chemistry Department, Azerbaijan University of Tarbiat Moallem, Tabriz, Iran
| | - R. Mohammadi
- Chemistry Department, Azerbaijan University of Tarbiat Moallem, Tabriz, Iran
| | | | - M. R. Rashidi
- Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - S. Davaran
- Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - M. Barshan
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | - S. E. Ranaei-Siadat
- Department of Biology, Faculty of Science, Ferdowsi University, Meshhad, Iran
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Alshetaili AS, Almutairy BK, Alshahrani SM, Ashour EA, Tiwari RV, Alshehri SM, Feng X, Alsulays BB, Majumdar S, Langley N, Kolter K, Gryczke A, Martin ST, Repka MA. Optimization of hot melt extrusion parameters for sphericity and hardness of polymeric face-cut pellets. Drug Dev Ind Pharm 2016; 42:1833-41. [PMID: 27080252 DOI: 10.1080/03639045.2016.1178769] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The aim of this study was to formulate face-cut, melt-extruded pellets, and to optimize hot melt process parameters to obtain maximized sphericity and hardness by utilizing Soluplus(®) as a polymeric carrier and carbamazepine (CBZ) as a model drug. Thermal gravimetric analysis (TGA) was used to detect thermal stability of CBZ. The Box-Behnken design for response surface methodology was developed using three factors, processing temperature ( °C), feeding rate (%), and screw speed (rpm), which resulted in 17 experimental runs. The influence of these factors on pellet sphericity and mechanical characteristics was assessed and evaluated for each experimental run. Pellets with optimal sphericity and mechanical properties were chosen for further characterization. This included differential scanning calorimetry, drug release, hardness friability index (HFI), flowability, bulk density, tapped density, Carr's index, and fourier transform infrared radiation (FTIR) spectroscopy. TGA data showed no drug degradation upon heating to 190 °C. Hot melt extrusion processing conditions were found to have a significant effect on the pellet shape and hardness profile. Pellets with maximum sphericity and hardness exhibited no crystalline peak after extrusion. The rate of drug release was affected mainly by pellet size, where smaller pellets released the drug faster. All optimized formulations were found to be of superior hardness and not friable. The flow properties of optimized pellets were excellent with high bulk and tapped density.
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Affiliation(s)
- Abdullah S Alshetaili
- a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA ;,b Department of Pharmaceutics, College of Pharmacy , Prince Sattam Bin Abdulaziz University , Alkharj , Saudi Arabia
| | - Bjad K Almutairy
- a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA
| | - Saad M Alshahrani
- b Department of Pharmaceutics, College of Pharmacy , Prince Sattam Bin Abdulaziz University , Alkharj , Saudi Arabia
| | - Eman A Ashour
- a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA
| | - Roshan V Tiwari
- a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA
| | - Sultan M Alshehri
- c Department of Pharmaceutics, College of Pharmacy , King Saud University , Riyadh , Saudi Arabia
| | - Xin Feng
- a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA
| | - Bader B Alsulays
- b Department of Pharmaceutics, College of Pharmacy , Prince Sattam Bin Abdulaziz University , Alkharj , Saudi Arabia
| | - Soumyajit Majumdar
- a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA
| | | | - Karl Kolter
- e R&D Project, Management Excipients, BASF SE , Ludwigshafen , Germany
| | - Andreas Gryczke
- f Global Development and Technical Marketing, BASF SE , Ludwigshafen , Germany
| | | | - Michael A Repka
- a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA ;,h Pii Center for Pharmaceutical Technology, The University of Mississippi, University , MS , USA
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Chang CW, Wong CY, Wu YT, Hsu MC. Development of a Solid Dispersion System for Improving the Oral Bioavailability of Resveratrol in Rats. Eur J Drug Metab Pharmacokinet 2016; 42:239-249. [DOI: 10.1007/s13318-016-0339-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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12
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Khan IU, Stolch L, Serra CA, Anton N, Akasov R, Vandamme TF. Microfluidic conceived pH sensitive core–shell particles for dual drug delivery. Int J Pharm 2015; 478:78-87. [DOI: 10.1016/j.ijpharm.2014.10.010] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Revised: 10/04/2014] [Accepted: 10/04/2014] [Indexed: 01/14/2023]
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Zou M, Wang C, Zhang X, Xu T, Han J, Zhang X, Cheng G. A suppository-base-matrix tablet for time-dependent colon-specific delivery system. BRAZ J PHARM SCI 2014. [DOI: 10.1590/s1984-82502014000300012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Our research has focused on the main design features and release performances of time-dependent colon-specific (TDCS) delivery tablets, which relies on the relative constancy that is observed in the small intestinal transit time of dosage forms. But inflammatory bowel disease（IBD）can affect the transit time, and usually results in watery stool. Compared to the TDCS and wax-matrix TDCS tablet, a promising time-dependent colon-specific delivery system was investigated. In our study, a suppository-base-matrix coated tablet was evaluated. Water soluble suppository-base helps the expansion of tablet, facilitates uniform film dissolution and achives high osmotic pressure. Combining the expansion of carboxymethyl starch sodium (CMS-Na) and the moisture absorption of NaCl, the coated TDCS tablet obtained a burst and targeted drug delivery system. A very good correlation between in vitro drug release and in vivo outcome was observed. This TDCS coated tablet provides a promising strategy to control drug release to the desired lower gastrointestinal region.
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14
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Abou Taleb MF. Radiation synthesis of multifunctional polymeric hydrogels for oral delivery of insulin. Int J Biol Macromol 2013; 62:341-7. [DOI: 10.1016/j.ijbiomac.2013.09.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2013] [Revised: 09/07/2013] [Accepted: 09/11/2013] [Indexed: 10/26/2022]
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Schrank S, Kann B, Windbergs M, Glasser BJ, Zimmer A, Khinast J, Roblegg E. Microstructure of Calcium Stearate Matrix Pellets: A Function of the Drying Process. J Pharm Sci 2013; 102:3987-97. [DOI: 10.1002/jps.23707] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Revised: 07/25/2013] [Accepted: 07/31/2013] [Indexed: 11/08/2022]
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Mahkam M, Mohammadi R, Siadat SOR. Synthesis and Evaluation of Biocompatible pH-Sensitive Hydrogels as Colon-Specific Drug Delivery Systems. J CHIN CHEM SOC-TAIP 2013. [DOI: 10.1002/jccs.200600096] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Zaid AN, Natour S, Qaddomi A, Abu Ghoush A. Formulation and in vitro and in vivo evaluation of film-coated montelukast sodium tablets using Opadry® yellow 20A82938 on an industrial scale. DRUG DESIGN DEVELOPMENT AND THERAPY 2013; 7:83-91. [PMID: 23430138 PMCID: PMC3573806 DOI: 10.2147/dddt.s37369] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Indexed: 11/23/2022]
Abstract
Purpose: The aim of this study was to formulate stable film-coated montelukast sodium (MS) tablets using Opadry® yellow 20A82938 (Montikast® tablets) and to evaluate their in vitro and in vivo release profile. Methods: MS core tablets were manufactured using a direct compression method. Opadry yellow 20A82938 aqueous coating dispersion was used as the film-coating material. Dissolution of the film-coated tablets was tested in 900 mL of 0.5% sodium lauryl sulfate solution and the bioequivalence of the tablets was tested by comparing them with a reference formulation – Singulair® tablets. In vitro–in vivo correlation was evaluated. The stability of the obtained film-coated tablets was evaluated according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. Results: The efficiency of the film coating was determined by subjecting the coated tablets to gastric pH and drug release was analyzed using high-performance liquid chromatography. The coated tablets had no obvious defects. MS release met the study criterion of not less than 80% dissolved after 30 minutes in 0.5% sodium lauryl sulfate solution. Statistical comparison of the main pharmacokinetic parameters clearly indicated no significant difference between test and reference in any of the calculated pharmacokinetic parameters. Level A correlation between in vitro drug release and in vivo absorption was found to be satisfactory. Conclusion: These findings suggest that aqueous film coating with Opadry yellow 20A82938 is an easy, reproducible, and economical approach for preparing stable MS film-coated tablets without affecting the drug-release characteristics.
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Affiliation(s)
- Abdel Naser Zaid
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
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Structure and properties of maize starch processed with a combination of α-amylase and pullulanase. Int J Biol Macromol 2013; 52:38-44. [DOI: 10.1016/j.ijbiomac.2012.09.030] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2012] [Revised: 09/20/2012] [Accepted: 09/27/2012] [Indexed: 11/22/2022]
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Singh G, Pai RS, Devi VK. Response surface methodology and process optimization of sustained release pellets using Taguchi orthogonal array design and central composite design. J Adv Pharm Technol Res 2012; 3:30-40. [PMID: 22470891 PMCID: PMC3312725 DOI: 10.4103/2231-4040.93565] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Furosemide is a powerful diuretic and antihypertensive drug which has low bioavailability due to hepatic first pass metabolism and has a short half-life of 2 hours. To overcome the above drawback, the present study was carried out to formulate and evaluate sustained release (SR) pellets of furosemide for oral administration prepared by extrusion/spheronization. Drug Coat L-100 was used within the pellet core along with microcrystalline cellulose as the diluent and concentration of selected binder was optimized to be 1.2%. The formulation was prepared with drug to polymer ratio 1:3. It was optimized using Design of Experiments by employing a 32 central composite design that was used to systematically optimize the process parameters combined with response surface methodology. Dissolution studies were carried out with USP apparatus Type I (basket type) in both simulated gastric and intestinal pH. The statistical technique, i.e., the two-tailed paired t test and one-way ANOVA of in vitro data has proposed that there was very significant (P≤0.05) difference in dissolution profile of furosemide SR pellets when compared with pure drug and commercial product. Validation of the process optimization study indicated an extremely high degree of prognostic ability. The study effectively undertook the development of optimized process parameters of pelletization of furosemide pellets with tremendous SR characteristics.
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Affiliation(s)
- Gurinder Singh
- Department of Pharmaceutics, Faculty of Pharmacy, Al-Ameen College of Pharmacy, Bangalore, Karnataka, India
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Sanka K, Bandari S, Jukanti R, Veerareddy PR. Colon-Specific Microparticles of Piroxicam: Formulation and Optimization Using 32Factorial Design. J DISPER SCI TECHNOL 2011. [DOI: 10.1080/01932691.2010.513275] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Zaid A, Fadda A, Nator S, Qaddumi A. Development and Stability Evaluation of Enteric Coated Diclofenac Sodium Tablets Using AquaPolish E. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2011. [DOI: 10.4333/kps.2011.41.4.211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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Cassidy CM, Tunney MM, Caldwell DL, Andrews GP, Donnelly RF. Development of novel oral formulations prepared via hot melt extrusion for targeted delivery of photosensitizer to the colon. Photochem Photobiol 2011; 87:867-76. [PMID: 21375536 DOI: 10.1111/j.1751-1097.2011.00915.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Colon-residing bacteria, such as vancomycin-resistant Enterococcus faecalis and Bacteroides fragilis, can cause a range of serious clinical infections. Photodynamic antimicrobial chemotherapy (PACT) may be a novel treatment option for these multidrug resistant organisms. The aim of this study was to formulate a Eudragit®-based drug delivery system, via hot melt extrusion (HME), for targeting colonic release of photosensitizer. The susceptibility of E. faecalis and B. fragilis to PACT mediated by methylene blue (MB), meso-tetra(N-methyl-4-pyridyl)porphine tetra-tosylate (TMP), or 5-aminolevulinic acid hexyl-ester (h-ALA) was determined, with tetrachlorodecaoxide (TCDO), an oxygen-releasing compound, added in some studies. Results show that, for MB, an average of 30% of the total drug load was released over a 6-h period. For TMP and h-ALA, these values were 50% and 16% respectively. No drug was released in the acidic media. Levels of E. faecalis and B. fragilis were reduced by up to 4.67 and 7.73 logs, respectively, on PACT exposure under anaerobic conditions, with increased kill associated with TCDO. With these formulations, photosensitizer release could potentially be targeted to the colon, and colon-residing pathogens killed by PACT. TCDO could be used in vivo to generate oxygen, which could significantly impact on the success of PACT in the clinic.
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Yue PF, Zheng Q, Liao MX, Zhang ZZ, Zhu WF. Process Optimization, Characterization, and Release Study In Vitro of an Intravenous Puerarin Lipid Micropheres Loaded with the Phospholipid Complex. J DISPER SCI TECHNOL 2010. [DOI: 10.1080/01932690903543600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Kuang SS, Oliveira JC, Crean AM. Microencapsulation as a Tool for Incorporating Bioactive Ingredients into Food. Crit Rev Food Sci Nutr 2010; 50:951-68. [DOI: 10.1080/10408390903044222] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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25
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Yue PF, Zheng Q, Wu B, Yang M, Wang MS, Zhang HY, Hu PY, Wu ZF. Process optimization by response surface design and characterization study on geniposide pharmacosomes. Pharm Dev Technol 2010; 17:94-102. [DOI: 10.3109/10837450.2010.516439] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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26
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Saboktakin MR, Tabatabaee RM, Maharramov A, Ramazanov MA. Design and characterization of chitosan nanoparticles as delivery systems for paclitaxel. Carbohydr Polym 2010. [DOI: 10.1016/j.carbpol.2010.05.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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27
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Karrout Y, Neut C, Wils D, Siepmann F, Deremaux L, Flament MP, Dubreuil L, Desreumaux P, Siepmann J. Peas starch-based film coatings for site-specific drug delivery to the colon. J Appl Polym Sci 2010. [DOI: 10.1002/app.32802] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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28
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Saboktakin MR, Tabatabaie RM, Maharramov A, Ramazanov MA. Synthesis and characterization of biodegradable chitosan beads as nano-carriers for local delivery of satranidazole. Carbohydr Polym 2010. [DOI: 10.1016/j.carbpol.2010.03.047] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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29
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Bassi P, Kaur G. pH modulation: a mechanism to obtain pH-independent drug release. Expert Opin Drug Deliv 2010; 7:845-57. [DOI: 10.1517/17425247.2010.491508] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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30
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Rhee YS, Lee JH, Lee BJ, Park ES. Controlled-Release Pelletized Dosage Forms Using the Extrusion-Spheronization Process. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2010. [DOI: 10.4333/kps.2010.40.s.103] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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31
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Youn YS, Lee JH, Jeong SH, Shin BS, Park ES. Pharmaceutical Usefulness of Biopharmaceutics Classification System: Overview and New Trend. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2010. [DOI: 10.4333/kps.2010.40.s.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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32
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Abstract
The objective of this study is to utilize the pH sensitivity of modified carboxymethyl starch (CMS) for oral delivery of insulin. The chemical modification of natural polymers by grafting has received considerable attention in recent years because of the wide variety of monomers available. Methacrylic-type polymeric prodrugs were synthesized by free radical copolymerization of methacrylic acid, poly(ethyleneglycol monomethyl ether methacrylate) (PEGMA), and carboxymethyl starch (CMS) in the presence of bis-acrylamide as a cross-linking agent (CA) and persulfate as an initiator. The pH sensitive nature and ability to control gel permeability indicate that these materials have significant potential for drug delivery applications. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). Insulin was entrapped in these gels, and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4). Drug release studies showed that the increasing content of MAA in the copolymer enhances hydrolysis in SIF. In these cases, the biological activity of insulin was retained. These results were used to design and improve protein release behavior from these carriers.
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Affiliation(s)
- Mehrdad Mahkam
- Chemistry Department, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran.
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Bushra R, Shoaib MH, Aslam N, Mehmood ZA, Hashmat D. Enteric coating of ibuprofen tablets (200 mg) using an aqueous dispersion system. BRAZ J PHARM SCI 2010. [DOI: 10.1590/s1984-82502010000100011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Ibuprofen is a propionic acid derivative that belongs to the class NSAIDs. Major adverse reactions associated with Ibuprofen are related to GIT and include peptic and mucosal ulcers, dyspepsia, severe gastric pain and bleeding, that results in excessive treatment failure. The goal of this study was to develop enteric coated ibuprofen tablets in order to avoid gastric mucosal irritation, diffusion of drug across mucosal lining and to let active ingredient be absorbed easily in small intestine. The formulation was developed and manufactured through the direct compression process, the simplest, easiest and most economical method of manufacturing. Enteric coating was done using an Opadry white subcoating and an aqueous coating dispersion of Acryl-Eze. Enteric coated formulation was subjected to disintegration and dissolution tests by placing in 0.1 M hydrochloric acid for 2 h and then 1 h in phosphate buffer with a pH of 6.8. About 0.04% of drug was released in the acidic phase and 99.05% in the basic medium. These results reflect that ibuprofen can be successfully enteric coated in order to prevent its release in the stomach and facilitate rapid release of the drug in the duodenum, due to the presence of superdisintegrant. Formulating this enteric coated tablets could increase patient compliance by decreasing adverse drug reactions (ADR S) associated with Ibuprofen therapy.
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34
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Shi X, Li J, Tang Y, Yang Q. pH-Sensitive mesoporous zirconium diphosphonates for controllable colon-targeted delivery. ACTA ACUST UNITED AC 2010. [DOI: 10.1039/c0jm00587h] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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35
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Gomez-Amoza J, Martinez-Pacheco R. Influence of microstructure on drug release from extrusion-spheronization pellets. J Drug Deliv Sci Technol 2010. [DOI: 10.1016/s1773-2247(10)50048-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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36
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Otero-Espinar F, Luzardo-Alvarez A, Blanco-Méndez J. Non-MCC materials as extrusion-spheronization aids in pellets production. J Drug Deliv Sci Technol 2010. [DOI: 10.1016/s1773-2247(10)50047-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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37
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Das S, Deshmukh R, Jha AK. Role of natural polymers in the development of multiparticulate systems for colon drug targeting. ACTA ACUST UNITED AC 2010. [DOI: 10.4103/0975-8453.59516] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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38
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Kuang SS, Oliveira JC, Crean AM. An Analysis of the Influence of Multiple Processing Factors on the Characteristics of Bioactive-Loaded Beads Prepared by Extrusion–Spheronisation. FOOD BIOPROCESS TECH 2009. [DOI: 10.1007/s11947-009-0308-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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39
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Yue PF, Yuan HL, Li XY, Yang M, Zhu WF. Process optimization, characterization and evaluation in vivo of oxymatrine-phospholipid complex. Int J Pharm 2009; 387:139-46. [PMID: 20005937 DOI: 10.1016/j.ijpharm.2009.12.008] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2009] [Revised: 11/26/2009] [Accepted: 12/04/2009] [Indexed: 12/30/2022]
Abstract
The objective of this study was to prepare oxymatrine-phospholipid complex (OMT-PLC) to enhance oral bioavailability of oxymatrine. A central composite design approach was used for process optimization. The physicochemical properties of the complex obtained by optimal parameters were investigated by means of differential scanning calorimetry (DSC), X-ray diffraction (XRD) and N-octanol/water partition coefficient. Compared with those of the physical mixture or oxymatrine, the hepatocytes permeability of oxymatrine-phospholipid complexes was studied. The concentrations of oxymatrine after oral administration of OMT-PLC at different time in rats were determined by HPCE. Multiple linear regression analysis for process optimization revealed that the acceptable OMT-PLC was obtained wherein the optimal values of X(1), X(2) and X(3) were 3, 60 degrees C and 3 h, respectively. The oxymatrine and phospholipids in the OMT-PLC were combined by non-covalent bond, not forming a new compound. The better hepatocytes permeability was obtained by the OMT-PLC. Pharmacokinetic parameters of the complex in rats were T(max) 2.17 h, C(max) 0.437 microg ml(-1), AUC(0-infinity) 9.43 microg h ml(-1), respectively. The bioavailability of oxymatrine in rats was increased remarkably after oral administration of OMT-PLC (p<0.05), compared with those of oxymatrine or the physical mixture. This was mainly due to an improvement of the solubility of OMT-PLC.
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Affiliation(s)
- Peng-Fei Yue
- Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
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40
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Saboktakin MR, Maharramov A, Ramazanov MA. pH-sensitive starch hydrogels via free radical graft copolymerization, synthesis and properties. Carbohydr Polym 2009. [DOI: 10.1016/j.carbpol.2009.02.004] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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41
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Zou M, Wang Y, Xu C, Cheng G, Ren J, Wu G. Wax-Matrix Tablet for Time-Dependent Colon-Specific Delivery System of Sophora Flavescens Aiton: Preparation and In Vivo Evaluation. Drug Dev Ind Pharm 2009; 35:224-33. [DOI: 10.1080/03639040802258854] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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42
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Abstract
pH-sensitive hydrogels are suitable candidates for oral delivery of therapeutic peptides, proteins, and drugs, due to their ability to respond to environmental pH changes. New pH-sensitive glycopolymers have been developed by free-radical polymerization of methacrylic acid and 6-acryloyl-glucose-1, 2, 3, 4-tetraacetate, using 1, 6-hexandiol diacrylate and 1, 6-hexandiol propoxylate diacrylate as cross-linking agents. The hydrogels were characterized by differential scanning calorimetry and FTIR. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). A model drug, olsalazine [3, 3'-azobis (6-hydroxy benzoic acid)] as an azo derivative of 5-aminosalicylic acid, was entrapped in these gels and the in vitro release profiles were established separately in both enzyme-free SGF and SIF. The drug-release profiles indicated that the amount of drug released depended on the degree of swelling. The hydrogels containing polar propoxylate groups were hydrolyzed rather easily.
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Affiliation(s)
- M Mahkam
- Chemistry Department, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran.
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43
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Mahkam M, Doostie L. The Relation Between Swelling Properties and Cross-Linking of Hydrogels Designed for Colon-Specific Drug Delivery. Drug Deliv 2008; 12:343-7. [PMID: 16302329 DOI: 10.1080/10717540590952627] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Copolymers of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA)-based hydrogels containing 5% and 10% of a cross-linking agent were studied as drug delivery systems. Terephthalic acid was covalently linked with HEMA, abbreviated as CA (cross-linking agent). Free radical cross-linking copolymerization of HEMA and methacrylic acid (MAA) in three different molar ratios, mixed with a particulate 3, 3-azobis (6-hydroxy benzoic acid) (ABHB) as an azo derivative of 5-aminosalicylic acid with the various ratios CA as cross-linking agent were carried out with using 2, 2, Azobisisobutyronitrile as initiator at the temperature range 60-70 degrees C. The compositions of the cross-linked three-dimensional polymers were determined by FTIR spectroscopy. Glass transition temperature of the network polymers was determined calorimetrically. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing an aqueous buffer solution (pH 7.4 and pH 1) at 37 degrees C. The drug-release profiles indicate that the amount of drug release depends on its degree of swelling and cross-linking.
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Affiliation(s)
- Mehrdad Mahkam
- Chemistry Department, Faculty of Science, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran.
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44
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Alvarez-Fuentes J, Fernández-Arévalo M, González-Rodríguez ML, Cirri M, Mura P. Development of Enteric-coated Timed-release Matrix Tablets for Colon Targeting. J Drug Target 2008; 12:607-12. [PMID: 15621686 DOI: 10.1080/10611860400013501] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
A new oral drug delivery system for colon targeting has been developed based on enteric-coated matrix tablets which suitably exploits both pH-sensitive and time-dependent functions. Matrix-tablets were prepared by direct compression of mixtures of hydroxyethylcellulose (HEC), a hydrophilic swellable polymer, with the inert insoluble ethylcellulose (EC) or micro-crystalline cellulose (MCC) polymers, in which theophylline, selected as model drug, was dispersed. Eudragit S100, a methacrylic acid copolymer soluble at pH 7, was used as pH-sensitive coating polymer. The influence of varying the cellulose-derivative combinations and their relative ratios as well as the level of the coating polymer was investigated. Surface morphology of the tablets was monitored by SEM analysis before and after the release test. The results of release studies, performed according to the USP basket method using a sequence of dissolution media simulating the gastrointestinal physiological pH variation, indicated that the Eudragit S100 enteric-coated matrix tablets were successful in achieving gastric resistance and timed-release of the drug, assuring an adequate lag time for the intended colonic targeting, followed by a controlled-release phase. The enteric-coating level emerged as the critical factor in determining the duration of the lag-phase, whereas the release rate mainly depended on the matrix composition. Formulations with higher HEC content showed a faster drug release rate than those with greater content in inert polymer and the MCC-HEC combinations were more effective than the corresponding EC-HEC ones. The best results were given by the 27% coated 1:0.3:0.7 (w/w) drug/MCC/HEC tablets, which, after a 260 min lag time, regularly released the drug, achieving about 90% of release after 10 h.
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Affiliation(s)
- J Alvarez-Fuentes
- Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Sevilla, C/Prof. García González, s/n, 41012 Sevilla, Spain
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45
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Fude C, Lei Y, Jie J, Hongze P, Wenhui L, Dongmei C. Preparation and In Vitro Evaluation of pH, Time-Based and Enzyme-Degradable Pellets for Colonic Drug Delivery. Drug Dev Ind Pharm 2008; 33:999-1007. [PMID: 17891587 DOI: 10.1080/03639040601150393] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
The preparation of pH-dependent, time-based and enzyme degradable pellets was investigated for use as an oral colonic drug delivery system. It was expected that drug would be released immediately once the pellets reached the colon. The pellets were prepared using extrusion-spheronizing equipment and subsequently coated with three layers of three functional polymers by an air-suspension technique. The core consisted of 5-aminosalicylic acid (5-ASA) as a model drug, CaP as an enzyme-degradable material and microcrystalline cellulose (MCC) as an additive. As far as the three coated layers were concerned, the outer layer was coated with Eudragit L30D-55 for protection against gastrointestinal juices, the intermediate layer was coated with ethylcellulose (EC) to inhibit drug release during passage through the small intestine, and the inner film was coated with pectin for swelling and enzyme-degradation, which required a 30, 10, and 12% weight gain, respectively. Several micromeritic properties of the core pellets, including particle size distribution, particle size, degree of circularity, and friability, were evaluated to investigate the effects of the formulations of the cores and preparation conditions. Also, dissolution testing of the cores showed that the presence of calcium pectinate (CaP) markedly increased the drug release rate from the cores, as determined by scanning electron microscopy (SEM). In-vitro release studies indicated that the coated pellets completely protected the drug release in 0.1 mol/L HCl, while the drug release was delayed for 3-4 hr in pH 6.8 PBS. A synergistic effect of enzyme dependence for the coated pellets was seen following removal of the coated layer and during contact with colonic enzymes. Consequently, it was possible to achieve colon-specific drug delivery using this triple-dependence system.
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Affiliation(s)
- Cui Fude
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang City, Liaoning, PR China.
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46
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Sergio AP, Isabel DSFDRC, José BM, Otero-Espinar FJ. Fast and Controlled Release of Triamcinolone Acetonide from Extrusion-Spheronization Pellets Based on Mixtures of Native Starch with Dextrin or Waxy Maize Starch. Drug Dev Ind Pharm 2008; 33:945-51. [PMID: 17891580 DOI: 10.1080/03639040601128720] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Pellets composed chiefly of inexpensive starches allow modulation of the rate of release of the poorly soluble drug triamcinolone acetonide in media of pH 1.2-6.8. Wheat- or maize-starch-based pellets with 20% of white dextrin release the drug in vitro almost completely within 20 min, while maize-starch-based pellets with 5-35% of waxy maize starch sustain gradual release over periods of 9-12 hr or longer when prepared using appropriate amounts of granulation fluid.
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Affiliation(s)
- Almeida-Prieto Sergio
- Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain
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47
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Yu TW, Chen RRL, Gau CS. Production of an Extremly Low Dose Procaterol HCl Preparation by Fluidized-Bed Coating Method: In Vitro and In Vivo Evaluation. Drug Dev Ind Pharm 2008; 32:651-60. [PMID: 16885120 DOI: 10.1080/03639040600623317] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
A convenient and reliable method to prepare procaterol HCl oral dosage form at an extremely low dosage (25 microg/cap) is presented in this paper. Procaterol HCl was mixed with the film-forming agent hydroxypropyl methylcellulose in an aqueous solution, which was then spray-coated on sugar spheres (Nu-pareil PG 20/25) to produce procaterol HCl pellets. The IR spectra of coated and noncoated pellets indicated that procaterol HCl was coated on the sugar spheres successfully with a weight increment less than 1%. Most of the coated pellets were able to pass through an 18-mesh screen with no agglomeration. The average weights of coated pellets filled inside of capsules were monitored during the filling process. A simple liquid chromatographic method was developed and validated for the assay and uniformity test of procaterol HCl in different dosage forms. The results of assay and content uniformity test for both in-house product and a commercial product, i.e., Meptin-mini tablet, were satisfied. The data of f(2) function and ANOVA analysis for the dissolution profiles of both procaterol HCl products suggested that they are pharmaceutical equivalent. In an in vivo study (n = 24), a single dose of 75 microg procaterol HCl was administrated to each volunteer and the plasma concentration of procaterol was determined by a LC/MS/MS method, developed by the same authors. There were no significant differences (p > 0.05) in the data of AUC(0-->16 h), AUC(0-->infinity), C(max), and MRT for both preparations. It is confirmed that the pellets capsule produced in this study is bioequivalent with Meptin-mini tablet.
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Affiliation(s)
- T-W Yu
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
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48
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Paker-Leggs S, Neau SH. Propranolol forms affect properties of Carbopol-containing extruded-spheronized beads. Int J Pharm 2008; 361:169-76. [DOI: 10.1016/j.ijpharm.2008.05.041] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2007] [Revised: 04/29/2008] [Accepted: 05/29/2008] [Indexed: 11/29/2022]
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49
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Yue PF, Zhang WJ, Yuan HL, Yang M, Zhu WF, Cai PL, Xiao XH. Process optimization, characterization and pharmacokinetic evaluation in rats of ursodeoxycholic acid-phospholipid complex. AAPS PharmSciTech 2008. [PMID: 18446498 DOI: 10.1208/s12249-008-9040-1.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
The purpose of this research was to study whether the bioavailability of ursodeoxycholic acid could be improved by administering ursodeoxycholic acid-phospholipid complex (UDCA-PLC) orally to rats. A central composite design approach was used for process optimization in order to obtain the acceptable UDCA-PLC. The physicochemical properties of the complex obtained by optimal parameters were investigated by means of scanning electron microscopy and X-ray diffraction. The pharmacokinetic parameters and bioavailability studies were conducted in rats of UDCA after oral administration of UDCA-PLC and UDCA tablet. Multiple linear regression analysis for process optimization revealed that the acceptable UDCA-PLC was obtained wherein the optimal values of X(1), X(2) and X(3) were 3, 60 degrees C and 3 h, respectively. The XRD studies of UDCA-PLC obtained by the optimal parameters demonstrated that UDCA and phospholipids in the UDCA-PLC were combined by non-covalent bonds, not form new compounds. But pharmacokinetic parameters of the complex in rats were T(max) 1.6 h, C(max) 0.1346 microg/ml, AUC(0-infinity) 11.437 microg x h/ml, respectively. The relative bioavailability of UDCA of UDCA-PLC was increased by 241%,compared with the reference ursodeoxycholic acid tablet.
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Affiliation(s)
- Peng-Fei Yue
- 302 Hospital of PLA&PLA Institute of Chinese Materia Medica, Beijing 100039, China
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50
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Dexter AF, Malcolm AS, Zeng B, Kennedy D, Middelberg APJ. Mixed system of Eudragit s-100 with a designed amphipathic peptide: control of interfacial elasticity by solution composition. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2008; 24:3045-3052. [PMID: 18275234 DOI: 10.1021/la703252r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
We report an interfacially active system based on an informational peptide surfactant mixed with an oppositely charged polyelectrolyte. The 21-residue cationic peptide, AM1, has previously been shown to respond reversibly to pH and metal ions at fluid interfaces, forming elastic films that can be rapidly switched to collapse foams or emulsions on demand. Here we report the reversible association of AM1 with the methacrylate-based anionic polymer Eudragit S-100. The strength of the association, in bulk aqueous solution, is modulated by added metal ions and by ionic strength. Addition of zinc ions to the peptide-polymer system promotes complex formation and phase separation, while addition of a chelating agent reverses the association. The addition of salt weakens peptide-polymer interactions in the presence or absence of zinc. At the air-water interface, Eudragit S-100 forms an elastic mixed film with AM1 in the absence of metal, under conditions where the peptide alone does not show interfacial elasticity. When zinc is present, the elasticity of the mixed film is increased, but the rate of interfacial adsorption slows due to formation of peptide-polymer complexes in bulk solution. An understanding of these interactions can be used to identify favorable foam-forming conditions in the mixed system.
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Affiliation(s)
- Annette F Dexter
- Centre for Biomolecular Engineering, School of Engineering and Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia QLD 4072 Australia
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