Pharmacokinetics

Paediatric drug development: are population models predictive of pharmacokinetics across paediatric populations?

by Massimo Cella

Genipin crosslinked drug-gelatin composite for drug transport and cytocompatibilty

by Dr. Goutam Thakur

Goutam Thakur, Analava Mitra, Amit Basak. Biomedical Engineering: Applications, Basis and Communications, 23 (2):113–118, 2011

Gelatin based drug carrier matrices have emerged as very promising class of delivery system. The purpose of this... more Gelatin based drug carrier matrices have emerged as very promising class of delivery system. The purpose of this investigation was to develop drug loaded gelatin based
gels (composites). Gelatin matrices were crosslinked with genipin, a naturally occurring crosslinker for the release of indomethacin. Indomethacin, a low molecular weight and moderately hydrophobic, anti-inflammatory agent was incorporated into the gelatin matrices to form drug loaded gel composites for the release study. The gels were subjected to temperature-dependent oscillatory rheology. The result showed pouring temperature in the range of ~31-34°C for the un-crosslinked gels while the crosslinked gels didn’t show crossover point. Gels were studied for surface morphology using scanning electron microscopy and a porous network structure was observed. The release of indomethacin from the gels indicated an initial increase in the release rate with the increase in drug concentrations. It was observed that drug composites with higher drug concentration, exhibited higher drug transport. Swelling and cross linking played crucial role in regulating the drug transport. Further, viability assay suggested biocompatibility of these matrices in vitro. Gel in vitro cell compatibility using live dead assay was evaluated with AH-927 cell line indicated normal cell proliferation without any harmful effect and thus suggesting appropriateness of crosslinked composites as potential drug carrier.

Keywords: Genipin, crosslinking, gelatin composite, drug release, cytocompatibility

Effect of trikatu pretreatment on the pharmacokinetics of pefloxacin administered orally in mountain Gaddi goats

by Madhukar Dama

The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal... more The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t 1/2 beta) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd(area)] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd(B)] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 microg/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals.

Lamoure J. Collaborative Patient Centered Care Model (CPCCM): Applicability to Bioequivalence.- (Oral Presentation and Abstract)

by Dr. Joel Lamoure

Lamoure J. Collaborative Patient Centered Care Model (CPCCM): Applicability to Bioequivalence. (Oral Presentation and... more Lamoure J. Collaborative Patient Centered Care Model (CPCCM): Applicability to Bioequivalence. (Oral Presentation and Abstract). Presented at Canadian Pharmacists Association 99th Annual Conference Montreal, Quebec, Canada. May 30,2011

Antibiotic Efficacy in Respiratory Tract Infections - Application of Pharmacokinetic and Pharmacodynamic Principles

by Stacy Collins

Author: Michael R Jacobs
Published in Touch US Respiratory Care 2006

Synthesis of novel hydroxypropyl methyl cellulose acrylate- A novel superdisintegrating agent for pharmaceutical applications

by Dr. Goutam Thakur

Saroj Roy, Kunal Pal, Goutam Thakur, Bala Prabhakar, Materials and Manufacturing Process,25: 1477–1481 (2010)

The current study deals with the synthesis of novel hydroxypropyl methyl cellulose acrylate (HPMCAA) by the process of... more The current study deals with the synthesis of novel hydroxypropyl methyl cellulose acrylate (HPMCAA) by the process of esterification of hydroxypropyl methyl cellulose and acryloyl chloride. The polymers were characterized by FTIR spectrophotometry, DSC, XRD and haemocompatibility studies. The microstructures of the HPMC and HPMCAA powders were studied under a scanning electron microscope. The powders were used as an excipient for the preparation of lactose tablets and their composition was varied from 2% to 8 % (w/w) of the total tablet weight. Disintegration studies for the tablets were carried out. The results indicated formation of a new product, HPMCAA, having properties different from HPMC. HPMCAA was found to be haemocompatible in nature. Disintegration tests indicated that HPMCAA could be tried as a superdisintegrating
agent.

Gelatin-based emulsion gels for diffusion-controlled release applications

by Dr. Goutam Thakur

Goutam Thakur, Muhammad Ali Naqvi, Dérick Rousseau, Kunal Pal, Analava Mitra, Amit Basak, Journal of Biomaterials Science: Polymer Edition 23: 645–661(2012)

Emulsion gels are now emerging as a new class of biomaterials for controlled release applications. Novel food-grade... more Emulsion gels are now emerging as a new class of biomaterials for controlled release applications. Novel food-grade emulsion gels consisting of indomethacin-loaded vegetable oil droplets dispersed within genipin-crosslinked gelatin-based hydrogels were characterized for their physical and drug release properties. Varying the weight ratio of the aqueous and oil phases between 5:1 and 5:5 was used to modulate construct swelling and drug release. The dispersed oil droplets generally became larger, more polydispersed and aggregated with an increase in oil fraction. Crosslinking with genipin increased the puncture strength of the gels vs. their uncrosslinked counterparts and was necessary to prevent breakdown. Swelling of the emulsion gels demonstrated Fickian behaviour at all gelatin: oil ratios. Indomethacin release followed Fickian diffusion at higher oil fractions only, demonstrating coupled Fickian and Super-Case II transport at lower oil ratios (5:1, 5:2 and 5:3). Overall, the introduction of a dispersed oil phase within a hydrogel was exploited for the release of hydrophobic bioactive compounds, with tailoring of composition used to significantly alter release kinetics.

Bridging the gap: ageing, pharmacokinetics and pharmacodynamics.

by Dominick Burton

Burton DG, Allen MC, Bird JL, Faragher RG.

Changes in pharmacokinetics and pharmacodynamics in elderly patients generally result in an increase in the incidence... more Changes in pharmacokinetics and pharmacodynamics in elderly patients generally result in an increase in the incidence of drug toxicity and adverse drug reactions. Molecular alterations associated with ageing could bring about biological changes, a consequence of which is an altered response to pharmacological agents. Unfortunately, research in this area has yet to progress beyond the cataloguing of the pharmacokinetic and pharmacodynamic changes observed in the elderly. Therefore, real progress in our understanding of pharmacogerontology could be achieved if it were possible to merge pharmacokinetic and pharmacodynamic studies with recent advances in our understanding of the causal processes bringing about ageing changes at the cellular level. Therefore, this review will focus on the mechanisms of ageing in the hope that the information will be of value to those planning independent studies.

Crosslinking of gelatin-based drug carriers by genipin induces changes in drug kinetic profiles in vitro

by Dr. Goutam Thakur

Goutam Thakur, Analava Mitra, Dérick Rousseau, Amit Basak, Siddik Sarkar, Kunal Pal ,Journal of Materials Science: Materials in Medicine, 22(1):115-123 (2011)

Hydrogels are extensively studied as carrier matrices for the controlled release of bioactive molecules. The aim of... more Hydrogels are extensively studied as carrier matrices for the controlled release of bioactive molecules. The aim of this study was to design gelatin-based hydrogels crosslinked with genipin and study the impact of crosslinking temperature (5, 15 or 25°C) on gel strength, microstructure, cytocompatibility, swelling and drug release. Gels crosslinked at 25°C exhibited the highest Flory–Rehner crosslink density, lowest swelling ratio and the slowest release of indomethacin (Idn, model anti-inflammatory drug). Diffusional exponents (n ) indicated non-Fickian swelling kinetics while drug transport was anomalous. Hydrogel biocompatibility, in vitro cell viability, cell cycle experiments with AH-927 and HaCaT cell lines indicated normal cell proliferation without any effect on cell cycle. Overall, these results substantiated the use of genipin crosslinked hydrogels as a viable carrier matrix for drug release applications