Mucoadhesive buccal patches of lornoxicam: II- in-vivo evaluation and clinical efficacy

Lornoxicam is a NSAID of the oxicam class and it has the same side effects of this group when taken orally. In attempts to avoid the systemic side effects of lornoxicam [e.g. gastric irritation] and to achieve sustained release of the drug, several buccal patch formulations containing lornoxicam were prepared using different polymers and were evaluated for in-vitro characteristics in part I of this study. In the current study, the selected formulations [based on the previous in-vitro data] are evaluated for in-vivo performance using experimental animals and clinical efficacy on human volunteers. Pharmacokinetic parameters were assessed following application of the selected patches in rabbits. A comparative clinical study was conducted on patients with post-operative pain and edema following maxillofacial operations. The results of the in-vivo animal experiment showed that lornoxicam formulated in different buccal patches was successfully delivered to the systemic circulation and showed high absolute bioavailability of lornoxicam. The clinical study results revealed that sodium carboxy methyl cellulose [NaCMC, 3%] formulation applied to the buccal mucosa was slightly better or equally effective to the orally administered commercial oxicam product [Feldene Flash tablets] in reducing pain level, swelling and tenderness within a period of 4 days with no observed side effects. These findings suggest that lornoxicam administered in this buccal patch may present a potential therapeutic use as a strong anti-inflammatory and analgesic agent

Improvement of solubility and dissolution rate of indomethacin by solid dispersions in gelucire 50/13 and PEG4000

The aim of this study was to prepare and characterize solid dispersions of water insoluble non steroidal anti-inflammatory drug, indomethacin [IND], with polyethylene glycol 4000 [PEG4000] and Gelucire 50/13 [Gelu.] for enhancing the dissolution rate of the drug. The solid dispersions [SDs] were prepared by hot melting method at 1:1, 1:2 and 1:4 drug to polymer ratios. Scanning electron microscopy [SEM], X-ray powder diffractometry [XRD] and differential scanning calorimetry [DSC] were used to examine the physical state of the drug. Furthermore, the solubility and the dissolution rate of the drug in its different systems were explored. The data from the XRD showed that the drug was still detectable in its solid state in all SDs of IND-Gelu and disappeared in case of higher ratio of IND-PEG4000. DSC thermograms showed the significant change in melting peak of the IND when prepared as SDs suggesting the change in crystallinity of IND. The highest ratio of the polymer [1:4] enhanced the drug solubility about 4 folds or 3.5 folds in case of SDs of IND-PEG or IND-Gelu., respectively. An increased dissolution rate of IND at pH 1.2 and 7.4 was observed when the drug was dispersed in these carriers in form of physical mixtures [PMs] or SDs. IND released faster from the SDs than from the pure crystalline drug or the PMs. The dissolution rate of IND from its PMs or SDs increased with an increasing amount of polymer

Clinical evaluation of oral insulin formulation in type-2 diabetic patients

The objective of this study was to assess the clinical efficacy of a single dose of insulin [100 IU] incorporated with a group of additives in enteric-coated, chitosan-coated capsules through its glucose lowering effect over a period of 12 hours. The capsules were administered orally to type-2 diabetic patients. The results were compared to those of oral administration of capsules of the same coating containing only insulin [100 IU] without additives, S.C. insulin injection [average dose 18 IU] and oral placebo. Ten patients with type-2 diabetes were enrolled in this blind, placebo-controlled, four-way crossover study. It was found that, capsules containing, only insulin resulted in a slight decrease in the mean blood glucose levels of the 10 patients compared to control especially in the period from 6 to 12 hours following administration. On the other hand, capsules containing insulin with additives showed a remarkable lowering of the blood glucose levels. Their effect started 3 hours following administration and sustained to the end of the experiment [12 h]. During the first 4 hours following administration was the reduction resulting from S.C. insulin was significantly higher than that produced by capsules containing insulin with additives. In the period from 4-7 hours, the effect of the capsules was comparable to that of S.C. insulin [no significant difference]. Beyond that [7-12 hours], there was a highly significant difference in favor of capsules. The relative bioavailability obtained by capsules containing only insulin was 3.43%, while that obtained by capsules containing insulin with additives was 18.54%