Factors Affecting Mechanism and Kinetics of Drug Release from Matrix-Based Oral Controlled Drug Delivery Systems

Varma, Manthena V.; Kaushal, Aditya Mohan; Garg, Alka B.; Garg, Sanjay

doi:10.2165/00137696-200402010-00003

Cited by 163 publications

(113 citation statements)

References 45 publications

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“…This is reflected by the large number of patents filed each year and by the commercial success of a number of novel drug delivery systems based on matrix technologies (1). In matrix devices, the drug is homogeneously dispersed in either a hydrophobic or hydrophilic polymer matrix.…”

Section: Introductionmentioning

confidence: 99%

Controlled Release Hydrophilic Matrix Tablet Formulations of Isoniazid: Design and In Vitro Studies

Hiremath

Saha

2008

AAPS PharmSciTech

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Abstract. The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using KorsmeyerPeppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f 2 metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/ HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

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Section: Introductionmentioning

confidence: 99%

Controlled Release Hydrophilic Matrix Tablet Formulations of Isoniazid: Design and In Vitro Studies

Hiremath

Saha

2008

AAPS PharmSciTech

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“…Thereby, through suitable mathematical models, it is possible to estimate the effect of system design parameters on the drug release kinetics (1)(2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Modeling of Progesterone Release from Poly(3-Hydroxybutyrate) (PHB) Membranes

et al. 2015

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Abstract. Poly(3-hydroxybutyrate) (PHB) biodegradable polymeric membranes were evaluated as platform for progesterone (Prg)-controlled release. In the design of new drug delivery systems, it is important to understand the mass transport mechanism involved, as well as predict the process kinetics. Drug release experiments were conducted and the experimental results were evaluated using engineering approaches that were extrapolated to the pharmaceutical field by our research group. Membranes were loaded with different Prg concentrations and characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). SEM images showed that membranes have a dense structure before and after the progesterone addition. DSC and FTIR allowed determining the influence of the therapeutic agent in the membrane properties. The in vitro experiments were performed using two different techniques: (A) returning the sample to the receptor solution (constant volume of the delivery medium) and (B) extracting total volume of the receptor solution. In this work, we present a simple and accurate Blumped^second-order kinetic model. This lumped model considers the different mass transport steps involved in drug release systems. The model fits very well the experimental data using any of the two experimental procedures, in the range 0≤t≤∞ or 0≤M t ≤M ∞ . The drug release analysis using our proposed approaches is relevant for establishing in vitro--in vivo correlations in future tests in animals.

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“…This is reflected by the large number of patents filed each year and by the commercial success of a number of extended release systems based on matrix technologies (2).…”

Section: Introductionmentioning

confidence: 99%

Polymer Percolation Threshold in HPMC Extended Release Formulation of Carbamazepine and Verapamil HCl

2010

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Abstract. The principles of the percolation theory were applied to further understand and design hydroxypropyl methylcellulose (HPMC) extended release matrix tablets containing carbamazepine and verapamil HCl. This statistical theory studies disordered or chaotic systems where the components are randomly distributed in a lattice. The application of this theory to study the hydration and drug release of hydrophilic matrices allows describing the changes in hydration and drug release kinetics of swellable matrices. The aim of this work was to study and develop extended release matrix formulations for carbamazepine and verapamil HCl, containing hypromellose (HPMC, METHOCEL™ Premium K100M CR) as rate controlling polymer using the concepts of percolation theory. The knowledge of the percolation threshold of the components of the matrix formulations contributes to improve their design. First, reducing the time to market and second, avoiding to formulate in the nearby of the percolation threshold, which will result in a lower variability. Therefore these formulations will be more robust when they are prepared at industrial scale. The HPMC percolation threshold for drugs with very different water solubilities was determined and it was shown that there was no significant influence of drug solubility on the HPMC critical concentration threshold (excipient percolation threshold). This may be related to the versatility and broad functionality of the swelling hydrophilic matrices.

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Factors Affecting Mechanism and Kinetics of Drug Release from Matrix-Based Oral Controlled Drug Delivery Systems

Cited by 163 publications

References 45 publications

Controlled Release Hydrophilic Matrix Tablet Formulations of Isoniazid: Design and In Vitro Studies

Controlled Release Hydrophilic Matrix Tablet Formulations of Isoniazid: Design and In Vitro Studies

Modeling of Progesterone Release from Poly(3-Hydroxybutyrate) (PHB) Membranes

Polymer Percolation Threshold in HPMC Extended Release Formulation of Carbamazepine and Verapamil HCl

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