COMPARATIVE PHARMACEUTICAL EVALUATION OF VARIABLE RETAIL PRICED MEDICINES CONTAINING BIOPHARMACEUTICAL CLASSIFICATION SYSTEM CLASS-II OR CLASS-IV DRUGS

The purpose of the present study is to highlight the discriminations if any, between the quality of low and high-cost medicines, which would help to select the right brand of medicine. In the present work, brands of medicines having high, medium, and low prices containing either of biopharmaceutical classification system class-II or class-IV drugs were comparatively evaluated for different pharmacopoeial standards as well as for biopharmaceutical classification system solubility and permeability. An ex vivo permeability test was carried out using a simple and non-invasive everted gut sac technique. Insignificant variation in pharmaceutical quality and permeability of the tested three types of brands was observed; however, the study could not consider the state of quality assurance facilities and parameters used while manufacturing these medicines. The study will help to make aware and assure medical and pharmacy practitioners and consumers for the selection of quality quality generic medicines.

Development of a BCS Class II Drug Microemulsion for Oral Delivery: Design, Optimization, and Evaluation

Our work is aimed at exploring the composition and the properties of microemulsion (ME), as a drug delivery system, to enhance the permeability across the gastrointestinal (GI) barrier of fenofibrate, a BCS class II drug. It is a prodrug that is converted rapidly after oral administration into a major active metabolite which is the fenofibric acid. It undergoes a nearly complete presystemic metabolism. Its main drawback is the low bioavailability of the metabolite. A quick selection of excipients was made based on the capacity of solubilization and the value of hydrophilic-lipophilic balance. The classical method of ME development was coupled with the factorial design in order to minimize the droplet size using a low concentration of surfactant. The optimized ME showed a droplet size of 48.5 nm and physical stability. The passive permeability evaluated using Sartorius was 1.6 times higher than that of the free drug. The ex vivo technique, performed using the everted gut sac model, showed a 2.5-fold higher permeability. This suggests that the carrier-mediated uptake/efflux may present the dominant transport mechanism of fenofibrate. The use of the excipients that inhibit GI P-glycoprotein may be a new perspective. Thus, this paper shows that the composition and the characteristics of ME may be explored to increase the permeability of fenofibrate across the GI membrane.

Fucoidan from Ascophyllum nodosum Suppresses Postprandial Hyperglycemia by Inhibiting Na+/Glucose Cotransporter 1 Activity

We previously demonstrated that fucoidan with a type II structure inhibited postprandial hyperglycemia by suppressing glucose uptake, but the mechanism remains elusive. Here, we aimed to assess whether the effect of glucose absorption inhibition was related to the basic structure of fucoidans and preliminarily clarified the underlying mechanism. Fucoidans with type II structure and type I structure were prepared from Ascophyllumnodosum (AnF) or Laminariajaponica (LjF) and Kjellmaniellacrassifolia (KcF), respectively. The effects of various fucoidans on suppressing postprandial hyperglycemia were investigated using in vitro (Caco-2 monolayer model), semi-in vivo (everted gut sac model), and in vivo (oral glucose tolerance test, OGTT) assays. The results showed that only AnF with a type II structure, but not LjF or KcF with type I structure, could inhibit the glucose transport in the Caco-2 monolayer and everted gut sac models. A similar result was seen in the OGTT of Kunming mice and leptin receptor-deficient (db/db) mice, where only AnF could effectively inhibit glucose transport into the bloodstream. Furthermore, AnF (400 mg/kg/d) treatment decreased the fasting blood glucose, HbA1c, and fasting insulin levels, while increasing the serum glucagon-like peptide-1 (GLP-1) level in obese leptin receptor-deficient (db/db) mice. Furthermore, surface plasmon resonance (SPR) analysis revealed the specific binding of AnF to Na+/glucose cotransporter 1 (SGLT1), which indicated the effect of AnF on postprandial hyperglycemia could be due to its suppression on SGLT1 activity. Taken together, this study suggests that AnF with a type II structure can be a promising candidate for hyperglycemia treatment.

Dye inhibition of phosphate transport in everted duodenal sacs of mice

Phenol Red has been widely used to test kidney function in man. Using the simple, everted gut sac technique has been observed to inhibit the phosphate transport by phenol red in the mouse intestine. We wanted to see if other similar organic anions are able to inhibit the phosphate transport across the mouse intestine. Both uptake and release of phosphate by the everted duodenal sacs of mice are inhibited by phenol red, bromocresol green and bromophenol blue. At the highest dose all the dyes were able to inhibit both influx and efflux significantly. Loss of phosphate from bathing solution is taken as influx and the gain of phosphate by the solution within the sac is taken efflux. At higher dosages a trend of increase in E/I% was noted. At the highest dose all the dyes were able to increase this parameter significantly over the control. Influx appears to be the primary process to be affected. Possible use of phenol red, on account of its safety in humans, as a hypophosphatemic agent is suggested.

Development of a New Ex Vivo Lipolysis-Absorption Model for Nanoemulsions

The use of lipid-based formulations (LBFs) in improving the absorption of poorly water-soluble drugs has now well established. Because the in vivo evaluation of LBFs is labor-intensive, in vitro or ex vivo approaches could provide advantages. In this study, a new ex vivo lipolysis-absorption model (evLAM) composed of an intestinal digestion system and an intestinal tissue system was developed to evaluate and predict the in vivo absorption performances of LBFs. Model factors, including the pH of the system and concentrations of d-glucose and pancreatic lipase, were investigated and optimized by a Box-Behnken design. To evaluate this new model, a lipid formulation of indomethacin, which was chosen based on preliminary studies of pseudo-ternary phase diagrams, emulsion droplets, and solubility, was further investigated by an in vivo pharmacokinetic study of rats, the everted gut sac model, and the evLAM, respectively. The absorption percentages obtained from the evLAM were much more similar to the data of rats in vivo than those from the everted gut sac model, showing a preferable in vitro-in vivo correlation (r = 0.9772). Compared with the conventional in vitro and in vivo methods, the evLAM, which allowed precise insights into the in vivo absorption characteristics without much time or a complicated process, could be a better tool for assessing LBFs of poorly water-soluble drugs.

Permeability Behavior of Nanocrystalline Solid Dispersion of Dipyridamole Generated Using NanoCrySP Technology

Nanocrystals research has been an area of significant interest lately, providing oral bioavailability benefits to solubility- and/or dissolution rate-limited drugs. Drug nanocrystals are generated using top-down or bottom-up technologies. Combination technologies (Nanoedge, Nanopure XP and SmartCrystal) have been recently developed to generate nanocrystals of improved properties. Our lab has also contributed in this field by providing a ‘novel’ platform technology, NanoCrySP, for the generation of nanocrystals. NanoCrySP-generated nanocrystals have improved the oral bioavailability of various molecules. In this study, we aim to assess the permeability behavior of nanocrystals generated by NanoCrySP. Three samples of Dipyridamole (DPM) drug were used in this study: (1) DPM (micron-sized powder), (2) nanocrystals of DPM (NS), generated by media milling (as control) and, (3) nanocrystalline solid dispersion containing DPM (NSD) in the matrix of mannitol (MAN), generated using NanoCrySP technology. In vitro (Caco-2 cell lines) and ex vivo (everted gut sac) studies were conducted in this work. Cellular permeability (Papp) from apical-to-basolateral side in Caco-2 cell monolayer was found to be in the order NS > NSD > DPM, which was the same as their apparent solubility values. Higher Papp from a basolateral-to-apical side suggested a significant contribution of the P-gp efflux transport for DPM, while NS exhibited much higher inhibition of the efflux mechanism than NSD. Both NS and NSD showed higher permeation from the jejunum region in the ex vivo everted gut sac study. Interestingly, Papp of NSD was similar to NS in ex vivo everted gut sac model, however, NSD showed higher mucoadhesion than NS and DPM in this study.