Effect of permeation enhancers in the mucoadhesive buccal patches of salbutamol sulphate for unidirectional buccal drug delivery.

The purpose of this work was to study the effect of various permeation enhancers on the permeation of salbutamol sulphate (SS) buccal patches through buccal mucosa in order to improve the bioavailability by avoiding the first pass metabolism in the liver and possibly in the gut wall and also achieve a better therapeutic effect. The influence of various permeation enhancers, such as dimethyl sulfoxide (DMSO), linoleic acid (LA), isopropyl myristate (IPM) and oleic acid (OA) on the buccal absorption of SS from buccal patches containing different polymeric combinations such as hydroxypropyl methyl cellulose (HPMC), carbopol, polyvinyl alcohol (PVA), polyvinyl pyrollidone (PVP), sodium carboxymethyl cellulose (NaCMC), acid and water soluble chitosan (CHAS and CHWS) and Eudragit-L100 (EU-L100) was investigated. OA was the most efficient permeation enhancer increasing the flux greater than 8-fold compared with patches without permeation enhancer in HPMC based buccal patches when PEG-400 was used as the plasticizer. LA also exhibited a better permeation enhancing effect of over 4-fold in PVA and HPMC based buccal patches. In PVA based patches, both OA and LA were almost equally effective in improving the SS permeation irrespective of the plasticizer used. DMSO was more effective as a permeation enhancer in HPMC based patches when PG was the plasticizer. IPM showed maximum permeation enhancement of greater than 2-fold when PG was the plasticizer in HPMC based buccal patches.

Efficacy and Safety of COX-2 Inhibitors in the Clinical Management of Arthritis: Mini Review.

In the clinical management of arthritis, the choice of nonsteroidal anti inflammatory drug (NSAID) remains confusing and controversial. A common practice on the choice of NSAID in clinical management of arthritis is the risk benefit ratio. The main objective of this review is to addresses the main arguments for the pharmacological and clinical use of COX-2 inhibitors in relation to nonselective NSAIDs for the clinical management of arthritis. This review concluded that, both NSAIDs and COX-2 inhibitors are equally effective and are associated with increased risk of GI, renal, and CV, adverse effects. Complete understanding of the patient's comorbid conditions and concomitant medications, coupled with precise monitoring during the treatment, may help to decrease the threat of adverse effects induced by nonselective NSAIDs and selective COX-2 inhibitors.

Mucoadhesive patches of Salbutamol sulphate for unidirectional buccal drug delivery: development and evaluation.

Mucoadhesive buccal patches of Salbutamol Sulphate were prepared using five different polymers (polyvinylpyrrolidone [PVP]), polyvinyl alcohol [PVA], water soluble chitosan [CH(WS)], acid soluble chitosan [CH(AS)], hydroxypropyl methyl cellulose [HPMC])in various proportions and combinations (CH(WS)/PVP/HPMC, CH(WS)/PVA/HPMC, CH(AS)/PVP/HPMC, and CH(AS)/PVA/HPMC). A 3(2) full factorial design was used to design the experiments. A total of 72 patches were prepared. Thickness of the patches ranged between 0.3±0.003 and 0.6±0.009 mm. Mass of the patches were in the range of 68.12±4.6 to 95.02±7.2 mg. Patches showed increased mass whenever PEG -400 was used as plasticizer. The surface pH of patches were acidic to neutral (pH 4-pH 7). Patches showed satisfactory drug loading efficiency (85%to 97%). Eight formulations(C9, C18, C27, C36, D9, D18, D27, and D36)-which showed high folding endurance- were selected for further characterization. Patches with PEG -400 showed higher swelling index when compared to PG. The residence time of the patches ranged between 115 min and 120 min. Formulation C18 showed the maximum in vitro drug release of 101.4 % over a period of 120 min. Formulations D36 and C36 were best fitted to Higuchi model. The remaining formulations were best fitted to the Korsmeyer-Peppas model. Drug permeation was fast and showed the similar profile as that of the in vitro drug release. Patches were stable, during and at the end of the accelerated stability study.

Formulation and in vitro-in vivo evaluation of ketoprofen-loaded albumin microspheres for intramuscular administration.

The objective of this work was to prepare and evaluate ketoprofen-loaded albumin microspheres for intramuscular administration. Microspheres were prepared by emulsion cross-linking method using a 2(3) factorial design and the effect of different factors on entrapment efficiency was determined. Microspheres were evaluated for entrapment efficiency, percentage yield, particle size and release behaviour. Selected formulations were then tested by differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Further they were analysed for residual solvents, syringeability and stability. Microspheres were then sterilized and bioavailability studies were carried out in New Zealand white rabbits. The physical characteristics of microspheres showed that they were suitable for IM administration. The sterilization technique adopted was adequate to maintain sterility. In vivo studies showed increase in C(max), AUC, t(1/2) and MRT (p < 0.05) administered in the form of microspheres. MRT of ketoprofen was almost 3.2-times in the form of microspheres. From these results it was concluded that the developed albumin microspheres of ketoprofen is a potential delivery system for once-a-day intramuscular administration.

Clinical evaluation of 5-fluorouracil from transdermal patches on EAC and DLA cell-induced tumors in mice.

The aim of the present study was formulate and clinically evaluate 5-fluorouracil (5-FU) transdermal patches. Cytotoxicity was measured by exposing cell suspensions to increasing concentrations of drug from 10-100 microg/ml and performing viable cell counts by the trypan blue exclusion method. Results confirmed 100 infinity g/ml and 50 microg/ ml of 5-FU to be cytotoxic to EAC and DLA cells. In mice, increase in the life span (ILS) by 87.1% with a maximum survival time of 30.5+/-1.87 days was found with EAC cell-induced tumors, with an ILS of 88.1% and a maximum survival time of 39.5+/-1.87 days for DLA cell-induced lesions with 5-FU transdermal patches. The results were statistically significant (p<0.01) compared to untreated controls. Pharmacokinetic studies in rabbits showed a t1/2 of 29+/-6 min, a Cmax (ng/ml) of 978.23, an AUC0-infinity (ng/ml/h) of 1213.73 +/-14 and a Tmax (h) of 0.5. 5-FU from transdermal patches exhibited a half-life of 95+/-0.5 min, a Cmax (ng/ml) of 863.25, an AUC0-infinity (ng/ml/h) of 1567+/-36 and a Tmax (h) of 1.5. Velcro protection jackets proved suitable in this study to stop mice licking, scratching and rubbing applied patches.