ASSESSMENT OF PERMEABILITY BEHAVIOR OF BERBERINE CHLORIDE ACROSS GOAT INTESTINAL MEMBRANE IN PRESENCE OF NATURAL BIOPOTENTIATOR CURCUMIN

The present study investigates the influence of co-administration of different concentrations (2, 6, and 10 mg) of curcumin on goat intestinal permeability of berberine chloride (BBC) using Franz diffusion cell. Data obtained in triplicate from permeability studies were used to calculate percentage cumulative drug release (% CDR), apparent permeability (Papp), flux (J) and enhancement ratio (ER). Co-administration of 6 mg concentration of curcumin with BBC was found to be optimum to enhance the permeability of BBC up to 23.92 ± 0.78 % CDR, over control (8.49 ± 1.45 % CDR). At the optimized concentration of curcumin, permeability characteristics were improved significantly compared to control. The present study reveals the beneficial effect of co-administration of curcumin (6 mg) to promote membrane permeability of BBC which would be expected to improve its bioavailability, thereby therapeutic efficacy. The effect could be attributed to curcumin-mediated inhibition of intestinal efflux pump P-gp, acting as an absorption barrier for BBC.

Chitosan-Based Oral Drug Delivery System for Peptide, Protein and Vaccine Delivery

Oral delivery is the most common and preferred route of drug administration due to its convenience and ease of administration. However, various factors such as poor solubility, low dissolution rate, stability, and bioavailability of many drugs remain an ongoing challenge in achieving desired therapeutic levels. The delivery of drugs must overcome various obstacles, including the acidic gastric environment, the presence of the intestinal efflux and influx transporters and the continuous secretion of mucus that protects the gastrointestinal tract (GIT). As the number and chemical diversity of drugs has increased, various strategies are required to develop orally active therapeutics. One of the approaches is to use chitosan as a carrier for oral delivery of peptides, proteins as well as vaccines delivery. Chitosan, a non-toxic N-deacetylated derivative of chitin appears to be under intensive progress during the last years towards the development of safe and efficient chitosan-based drug delivery systems. This polymer has been recognised as a versatile biomaterial because of its biodegradability, biocompatibility, and non-toxicity. This chapter reviews the physicochemical characteristics of chitosan and the strategies that have been successfully applied to improve oral proteins, peptides, and vaccines bioavailability, primarily through various formulation strategies.

A Physiologically-Based Pharmacokinetic Model of Trimethoprim for MATE1, OCT1, OCT2, and CYP2C8 Drug–Drug–Gene Interaction Predictions

Trimethoprim is a frequently-prescribed antibiotic and therefore likely to be co-administered with other medications, but it is also a potent inhibitor of multidrug and toxin extrusion protein (MATE) and a weak inhibitor of cytochrome P450 (CYP) 2C8. The aim of this work was to develop a physiologically-based pharmacokinetic (PBPK) model of trimethoprim to investigate and predict its drug–drug interactions (DDIs). The model was developed in PK-Sim®, using a large number of clinical studies (66 plasma concentration–time profiles with 36 corresponding fractions excreted in urine) to describe the trimethoprim pharmacokinetics over the entire published dosing range (40 to 960 mg). The key features of the model include intestinal efflux via P-glycoprotein (P-gp), metabolism by CYP3A4, an unspecific hepatic clearance process, and a renal clearance consisting of glomerular filtration and tubular secretion. The DDI performance of this new model was demonstrated by prediction of DDIs and drug–drug–gene interactions (DDGIs) of trimethoprim with metformin, repaglinide, pioglitazone, and rifampicin, with all predicted DDI and DDGI AUClast and Cmax ratios within 1.5-fold of the clinically-observed values. The model will be freely available in the Open Systems Pharmacology model repository, to support DDI studies during drug development.