FORMULATION OPTIMIZATION AND CHARACTERIZATION OF AQUEOUS INJECTION CONTAINING POORLY SOLUBLE DRUG USING MIXED HYDROTROPIC SOLUBILIZATION

Objective: Mefenamic acid (MFA) is an NSAID that exhibits anti-inflammatory analgesic and antipyretic activity. Peak plasma levels are attained in 2-4 h and the elimination half-life approximates 2 h, repetitive administration of tablets for 3-5 times a day is desired. It is supplied only in the form of tablets for oral administration. In acute conditions drug administered parenterally could give rapid relief from severe symptoms like pain. Thus, formulation of injectable formulation of MFA could be better alternative compared to conventional tablet dosage form. The low aqueous solubility of MFA precludes its use in parenteral formulation development. Methods: In this work attempt were made to enhance the aqueous solubility of mefenamic acid using mixed solvency technique. For that different hydrotropic agents such as Urea, Sodium acetate, sodium benzoate, sodium citrate and their blends were evaluated. Optimal concentration of hydrotropic agent in blend was determined using D-optimal mixture experimental design. The optimized bled was used to develop the aqueous injection of mefenamic acid. The developed injection was subjected for various quality control tests and stability of developed formulation was also evaluated. Results: The aqueous solubility in optimized blend of hydrotropic agent batches (U: SA: SB: SC, 4:4:23:9 %w/v) showed 835.71-fold compared to MFA solubility in distilled water. The quality control tests for parenteral formulation and accelerated stability study were found to be within prescribed limits and stable. Conclusion: The inadequate solubility of MFA was overcome, and aqueous injection was successfully developed which can be serve as cost effective treatment in various indications.

A therapeutic journey of potential drugs against COVID-19

Coronavirus disease (CoVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) scrambles the world by infecting millions of peoples all over the globe. It has caused tremendous morbidity, mortality and greatly impacted the lives and economy worldwide as an outcome of mandatory quarantines or isolations. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Physicians and researchers throughout the world are working to understand the pathophysiology to expose the conceivable handling regimens and to determine the effective vaccines and/or therapeutic agents. Some of them re-purposed drugs for clinical trials which were primarily known to be effective against the RNA viruses including MERS-CoV and SARS-CoV-1. In the absence of a proven efficacy therapy, the current management use therapies based on antivirals, anti-inflammatory drugs, convalescent plasma, anti-parasitic agents in both oral and parenteral formulation, oxygen therapy and heparin support. What is needed at this hour, however, is a definitive drug therapy or vaccine. Different countries are rushing to find this, and various trials are already underway. We aimed to summarized the potential therapeutic strategies as a treatment options for COVID-19 that could be helpful to stop further spread of SARS-CoV-2 by effecting its structural components or modulation of immune response and also discusses the leading drugs/vaccines, which were considered as potential agents for controlling this pandemic.

Designing a Formulation of the Nootropic Drug Aniracetam Using 2-Hydroxypropyl-β-Cyclodextrin Suitable for Parenteral Administration

The nootropic drug aniracetam is greatly limited in its application by low aqueous solubility and a poor oral bioavailability. The primary aim of this study was to design a parenteral formulation of aniracetam that can be administered intravenously. Complexation of aniracetam with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated as a strategy to enhance solubility. A phase solubility analysis was performed to quantify the extent of improvement. An 819% increase in the solubility of aniracetam was obtained, reaching 36.44 mg/mL. This marked increase enables aniracetam to exist in an aqueous solvent at levels sufficient for parenteral dosing. A stability test was then devised using a design of experiment approach. The aniracetam-HP-β-CD formulation was subjected to different relative humidity and temperature and cyclodextrin concentrations over a 12-week period. Key changes in FTIR vibrational frequencies suggest the benzene moiety of aniracetam was introduced into the hydrophobic cavity of HP-β-CD. These results are highly supportive of the formation of a predictable 1:1 molar stoichiometric inclusion complex, explaining the improvement seen in physiochemical properties of aniracetam following formulation with HP-β-CD. This novel formulation of aniracetam suitable for parenteral administration will have utility in future studies to further elucidate the pharmacokinetics of this drug.