Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.
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 Korsmeyer-Peppas 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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ABSTRACT: Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using karaya gum (K) alone or in combination with locust bean gum (LB) and hydroxypropyl methylcellulose (H). Methods: Matrix tablets of DTZ were prepared at different ratios of drug:gum (1:1, 1:2, and 1:4) and of the gum blends (K, K/LB, K/H and K/LB/H) by direct compression. The matrix tablets were evaluated for hardness, friability, in vitro release and drug content. The formulations were also characterised by scanning electron microscopy (SEM), Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). A commercial diltiazem hydrochloride product Dilzem SR, was used as a reference for comparison. Results: Tablets with only K or K/H had the highest mean dissolution time (MDT), the least dissolution efficiency (DE, 12 %), and released drug by swelling, diffusion and erosion mechanisms. Karaya gum or combinations with locust bean gum sufficiently controlled drug release, while combinations of KH and KLBH exhibited high and low drug release efficiency, respectively. SEM images of the tablets before and after dissolution showed morphological changes on the tablet surface while FTIR and DSC studies indicate that there was no chemical interaction between the drug and the polymers. Three of the formulations compared well with the reference (p < 0.05) in terms of release characteristics. Conclusion: The results of the study demonstrate that karaya gum alone or in suitable combination with locust bean gum and hydroxypropyl methylcellulose is suitable for formulating sustained-release matrix tablets of diltiazem.Tropical Journal of Pharmaceutical Research (ISSN: 1596-5996) Vol 9 Num 3.