Effects of various penetration enhancers on percutaneous absorption of piroxicam from emulgels

A suitable emulgel formulation of piroxicam was prepared and its percutaneous permeation was investigated using Wistar rat skin and diffusion cell technique. The concentrations of the drug in receptor phase of diffusion cells were measured using HPLC method. The effect of three types of penetration enhancers (Myrj 52, cineol and Transcutol P) with different concentrations on transdermal permeation of the drug was also evaluated. Flux, Kp and enhancement ratios (ERs) of piroxicam in the presence of enhancers was measured and compared with emulgel base alone and simple commercial gel. The results showed a significant enhancement in the flux from emulgel base compared to hydroalcoholic gel formulation (9.91 folds over simple gel). The highest enhancement ratio (ER=3.11) was observed for Myrj 52 at the concentration of 0.25%. Higher concentrations of Myrj 52did not show any enhancement in the drug flux due to micelle formation and solubilization of the drug by micelles. The increase in solubility, in turn, increases the saturated concentration and reduces the thermodynamic activity of the drug. Transcutol® P with concentrations higher than 0.25% w/w showed burst transportation of the drug through the skin. All concentrations of cineol and Transcutol did not show any enhancing effects over emulgel base alone (ER <1)

Poboljšanje fizičko-mehaničkih svojstava karbamazepina prekristalizacijom pri različitim pH

The morphology of crystals has an appreciable impact on the physicochemical properties of drugs. Drug properties such as flowability, dissolution, hardness and bioavailability may be affected by crystallinity behaviors of drugs. The objective of this study was to achieve improved physicomechanical properties of carbamazepine powder through recrystallization from aqueous solutions at different pH values. For this purpose, carbamazapine was recrystallized from aqueous solutions at different pH values (1, 7, 11). The morphology of crystals was investigated using scanning electron microscopy; X-ray powder diffraction (XRPD) was used to identify polymorphism; thermodynamic properties were analyzed using differential scanning calorimetery (DSC). Dissolution was determined using USP dissolution apparatus. Mechanical behavior of recrystallized carbamazepine powders was investigated by making tablets under different compaction pressures and measuring their hardness. SEM studies showed that carbamazepine crystallization in different media affected the morphology and size of carbamazepine crystals. The shape of carbamazepine crystals changed from flaky or thin plate-like to needle-shaped. XRPD and DSC results ruled out any crystallinity changes occurring due to the temperature or pH of crystallization media. The crushing strength of tablets indicated that all the recrystallized carbamazepine samples had better compactibility than the original carbamazepine powder. In vitro dissolution studies of carbamazepine samples showed a higher dissolution rate of carbamazepine crystals obtained from media with pH 11 and 1. Carbamazepine particles recrystallized from aqueous solutions of different pH values (all media) appeared to have superior mechanical properties to those of the original carbamazepine sample.Morfologija kristala ima značajan utjecaj na fizičko-mehanička svojstva lijekova. Kristaliničnost može utjecati na tečnost, oslobađanje, tvrdoću i bioraspoloživost lijekova. Cilj ovog rada bio je poboljšati fizičko-mehanička svojstva praha karbamazepina prekristalizacijom iz vodenih otopina pri različitim pH vrijednostima (1, 7 i 11). Fizičko-mehanička svojstva prekristaliziranog karbamazepina određivana su na sljedeći način: morfologija kristala ispitivana je pretražnom elektronskom mikroskopijom, polimorfi su identificirani rendgenskom difrakcijom praha (XRPD), a termodinamička svojstva analizirana su diferencijalnom pretražnom kalorimetrijom (DSC). Topljivost je određena pomoću aparata prema USP. Mehanička svojstva prekristaliziranog karbamazepina ispitivana su tijekom tabletiranja pri različitim tlakovima i mjerenjem tvrdoće nastalih tableta. SEM ispitivanja pokazala su da kristalizacija karbamazepina iz različitih medija utječe na morfologiju i veličinu kristala. Oblik kristala mijenjao se od pahuljastog ili pločastog do igličastog. Rezultati dobiveni XRPD i DSC metodama isključili su promjene kristaliničnosti zbog temperature ili pH medija. Mjerenjem lomljivosti tableta utvrđeno je da su svi prekristalizirani uzorci karbamazepina bili kompaktniji od polaznog praškastog uzorka. Ispitivanja topljivosti in vitro pokazala su da su kristali dobiveni iz otopine s pH 11 i 1 topljiviji. Uzorci karbamazepina dobiveni prekristalizacijom iz vodenih otopina različite pH vrijednosti imali su bolja mehanička svojstva od originalnog uzorka karbamazepina

Different experimental approaches in modelling cataractogenesis: An overview of selenite-induced nuclear cataract in rats

Cataract, the opacification of eye lens, is the leading cause of blindness worldwide. At present, the only remedy is surgical removal of the cataractous lens and substitution with a lens made of synthetic polymers. However, besides significant costs of operation and possible complications, an artificial lens just does not have the overall optical qualities of a normal one. Hence it remains a significant public health problem, and biochemical solutions or pharmacological interventions that will maintain the transparency of the lens are highly required. Naturally, there is a persistent demand for suitable biological models. The ocular lens would appear to be an ideal organ for maintaining culture conditions because of lacking blood vessels and nerves. The lens in vivo obtains its nutrients and eliminates waste products via diffusion with the surrounding fluids. Lens opacification observed in vivo can be mimicked in vitro by addition of the cataractogenic agent sodium selenite (Na2SeO3) to the culture medium. Moreover, since an overdose of sodium selenite induces also cataract in young rats, it became an extremely rapid and convenient model of nuclear cataract in vivo. The main focus of this review will be on selenium (Se) and its salt sodium selenite, their toxicological characteristics and safety data in relevance of modelling cataractogenesis, either under in vivo or in vitro conditions. The studies revealing the mechanisms of lens opacification induced by selenite are highlighted, the representatives from screening for potential anti-cataract agents are listed

Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract

Cataract is one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Mechanisms related to glucose toxicity, namely oxidative stress, processes of non-enzymatic glycation and enhanced polyol pathway significantly contribute to the development of eye lens opacity under conditions of diabetes. There is an urgent need for inexpensive, non-surgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in the prevention of cataract since flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of diabetic cataract. In the present paper, natural flavonoids are reviewed as potential agents that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification. In addition, the bioavailability of flavonoids for the lens is considered