A possible alternative to Opiorphin and its stable analogues for treating fibromyalgia pain: A clinical hypothesis.

The work aimed to explore the clinical hypothesis on the possible alternative to Opiorphin and its stable analogues for treating fibromyalgia pain. Fibromyalgia is a condition characterized by chronic pain triggered by an interplay of biological and psychosocial variables, although the exact pathogenesis is still controversial. Standard therapy for low threshold tender point pain includes NSAIDs and opioid analgesics, both of which have serious adverse profiles after long-term exposure, highlighting the need for an intermediate compound capable of bridging the gap between NSAIDs and opioid analgesics. Opiorphin is an anti-nociceptive modulator which inhibits the enzyme responsible for the degradation of natural endogenous opioid neuropeptides. This paper hypothesizes and concludes that Opiorphin and its stable analogues (Sialorphine, STR-324) can be an alternative for the treatment of chronic long-standing low-threshold tender point pain associated with fibromyalgia.

Influence of trazodone on the pharmacodynamics and pharmacokinetics of pioglitazone.

BACKGROUND: These days, poly pharmacy is very common for the treatment of multiple diseases and majority of drugs were metabolized with CYP 450 enzymes. Diabetes mellitus is such a disorder, which requires continuous therapy for the control of blood glucose concentration. Depression was quite common in diabetic patients. Therefore, multiple drugs required to treat diabetes mellitus and depression. Simultaneous administration of these drugs leads to drug interaction. Pioglitazone and trazodone metabolized by CYP3A4 enzymes which may lead to potential drug interaction. OBJECTIVES: This study aimed to find the influence of trazodone on the pharmacokinetics & pharmacodynamics of pioglitazone in normal & diabetic rats, also on rabbits and subsequently effectiveness and safety of the combination was evaluated. METHODS AND MATERIAL: Blood glucose concentration was determined by Glucose oxidase/peroxidase method in normal and diabetic rats. Diabetes was induced with Streptozotocin at a dose of 55 mg/kg body weight. Serum pioglitazone concentration was estimated by high performance liquid chromatography method for pharmacokinetic data. The values were expressed as Mean ± Standard Error Mean (SEM), GraphPad Prism 3.0 (San Diego, California, USA) software was used to express the data. Student's paired 't' test was used to determine the significance. RESULTS: Pioglitazone produces hypoglycaemia in normal rats with a maximum decrease of 36.78 % ± 0.81 at 3 hours interval and anti-hyperglycaemic activity in diabetic rats with maximum reduction of 45.13 % ± 1.52 at 2 hours interval. Trazodone altered the pharmacokinetics of pioglitazone and improved the pioglitazone hypoglycaemic effect. CONCLUSION: Trazodone apparently produced pharmacokinetic interaction with pioglitazone which might be by attenuating the metabolism of pioglitazone. Therefore, care should be taken in simultaneous therapy with pioglitazone and trazodone.

Designing of dexamethasone sodium phosphate ocular films for madras eye: In vitro and in vivo evaluation.

The main intention of the current investigation was to fabricate ocular films of Dexamethasone sodium phosphate (DSP) impregnated in rate controlling membrane and to characterize in vitro and in vivo (iv-iv). DSP release was regulated by HPMC K4M and ethyl cellulose (EC) and dimethyl sulfoxide (DMSO) as a permeability enhancer. DSP suitability with polymers was observed by DSC and FT Infrared spectroscopic readings. The fabricated DSP ocular films were examined for physicochemical tests, in vitro discharge and in vivo infusion in rabbits. The improved formulation (F-8) was proved its stability under stressed storage conditions. The fabricated ocular films process acceptable physical characters with DSP release in a controlled manner. The optimized DSP films were intact even in stressed storage situations. It was concluded that the fabricated films effectively hold the DSP at the programmed site for the desired period of time and exhibit expected pharmacodynamics actions.

A Cost Effective (QbD) Approach in the Development and Optimization of Rosiglitazone Maleate Mucoadhesive Extended Release Tablets -In Vitro and Ex Vivo.

Purpose: The purpose of the study was to develop and optimize rosiglitazone maleate mucoadhesive extended-release tablets by quality by design (QbD) approach. Based on QTPP (quality target product profile) CQAs (critical quality attributes) were identified. Methods: Failure mode and effects analysis (FMEA) method were adopted for risk assessment. Risk analysis by the evaluation of formulation and process parameters showed that the optimizing the levels of polymers could reduce high risk to achieve target profile. Drug-excipient compatibility studies by Fourier transforms infra-red and DSC studies showed that the drug was compatible with the polymers used. Design of experiment (DoE) performed by Sigma tech software, Carbopol 934P and sodium carboxymethyl cellulose (SCMC) were identified as independent variables and hardness, drug release at 12 hours and ex vivo mucoadhesion time were adopted as responses. Contour plots generated from the software were used for identification of design space. Results: Carbopol 934P and SCMC had positive and negative effects respectively on the selected responses. Higher the concentration of Carbopol 934P and lower the concentration of SCMC mucoadhesive extended release criteria could be achieved. Drug release kinetics followed first order release with Higuchi diffusion and Fickian diffusion. Ex vivo mucoadhesion test on goat stomach mucosa indicated that adhesion time increased at higher concentrations of Carbopol 934P. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values, confirmed by calculating standard error. Conclusion: It has been concluded that the application of QbD in the optimization reduced the number of trials to produce a cost-effective formula.