Solubility-permeability interplay of hydrotropic solubilization of piroxicam.

OBJECTIVES: In this research paper, an investigation has been made to assess the simultaneous effect of a solubility enhancement approach, i.e., hydrotropy on the solubility and apparent permeability of piroxicam. The solubility of piroxicam (PRX) a BCS (biopharmaceutics classification system) class II drug has been increased using a mixed hydrotropy approach. This study is based on identifying the pattern of solubility-permeability interplay and confirming whether every solubility gain results in a concomitant decrease in permeability or permeability remains unaffected. METHOD: Solid dispersions of PRX were formulated using two hydrotropes, viz., sodium benzoate (SB) and piperazine (PP) by solvent evaporation method. A comprehensive 32factorial design was employed to study the effect of hydrotropes on the solubility and permeability of PRX. Subsequently, PRX tablets containing these solid dispersions were formulated and evaluated. KEY FINDINGS: SB and PP displayed a significant increase in the solubility of PRX ranging from 0.99 to 2.21 mg/mL for F1-F9 batches attributed to the synergistic effect of hydrotropes. However, there is a reduction in PRX permeability with increasing hydrotrope levels. The decline in permeability was notably less pronounced compared to the simultaneous rise in aqueous solubility of PRX. CONCLUSION: An evident tradeoff between permeability and solubility emerged through the mixed hydrotropic solubilization for PRX. As PRX has generally higher intrinsic permeability, it has been assumed that this permeability loss will not affect the overall absorption of PRX. However, it may affect the absorption of drugs with limited permeability. Therefore, solubility permeability interplay should be investigated during solubility enhancement.

A Clinical Insight on New Discovered Molecules and Repurposed Drugs for the Treatment of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began churning out incredulous terror in December 2019. Within several months from its first detection in Wuhan, SARS-CoV-2 spread to the rest of the world through droplet infection, making it a pandemic situation and a healthcare emergency across the globe. The available treatment of COVID-19 was only symptomatic as the disease was new and no approved drug or vaccine was available. Another challenge with COVID-19 was the continuous mutation of the SARS-CoV-2 virus. Some repurposed drugs, such as hydroxychloroquine, chloroquine, and remdesivir, received emergency use authorization in various countries, but their clinical use is compromised with either severe and fatal adverse effects or nonavailability of sufficient clinical data. Molnupiravir was the first molecule approved for the treatment of COVID-19, followed by Paxlovid™, monoclonal antibodies (MAbs), and others. New molecules have variable therapeutic efficacy against different variants or strains of SARS-CoV-2, which require further investigations. The aim of this review is to provide in-depth information on new molecules and repurposed drugs with emphasis on their general description, mechanism of action (MOA), correlates of protection, dose and dosage form, route of administration, clinical trials, regulatory approval, and marketing authorizations.

A Comprehensive Investigation Regarding the Differentiation of the Procurable COVID-19 Vaccines.

COVID-19 caused by coronavirus SARS-CoV-2 became a serious threat to humankind for the past couple of years. The development of vaccine and its immediate application might be the only to escape from the grasp of this demoniac pandemic. Approximately 343 clinical trials on COVID-19 vaccines are ongoing currently, and almost all countries are motivating ongoing researches at warp speed for the development of vaccines against COVID-19. This review explores the progress in the development of the vaccines, their current status of ongoing clinical research, mechanisms, and regulatory approvals. Many pharmaceutical companies are already in the endgame for manufacturing various vaccines of which some are already being marketed across the globe, while others are yet to get approval for marketing. The primary aim of this review is to compare regulatory accepted vaccines in terms of their composition, doses, regulatory status, and efficacy. The study is conducted by grouping into approved and unapproved vaccines for marketing. Different routes of administration of vaccines along with the efficacy of the routes are also presented in the review. A wide range of database and clinical trial data is reviewed for sorting out the information on different vaccines. Unfortunately, many mutations (alpha, beta, gamma, delta, kappa, omicron etc.) of SARS-CoV-2 have attacked people in very short time, which is the great challenge for investigational vaccines. Moreover, some vaccines like Pfizer's BNT162, Oxford's ChAdOx1, Moderna's mRNA-1273, and Bharat Biotech's Covaxin have got regulatory approval in some countries for its distribution which may prove to stand tall against the pandemic.

Pathophysiology and inhibition of cholesteryl ester transfer protein for prevention of cardiovascular diseases: An update.

The enzyme cholesteryl ester transfer protein (CETP), involved in cholesterol metabolism and transportation, is one of the main causes of cardiovascular (CV) disease (CVD). When the CETP concentration is decreased by CETP inhibitors (e.g., anacetrapib, torcetrapib, obicetrapib, etc.), high-density lipoprotein (HDL) particles are formed and low-density lipoprotein (LDL) is decreased along with cholesterol transportation alteration, which reduces the development of atherosclerosis. Here, we discuss the role of CETP inhibitors in reducing well-known 'bad' cholesterols and the current status of trials of different CETP inhibitors, their adverse effects, and limitations, as well as the pathophysiology of CETP.

Lipids for Taste masking and Taste assessment in pharmaceutical formulations.

Pharmaceutical products often have drawbacks of unacceptable taste and palatability which makes it quite difficult for oral administration to some special populations like pediatrics and geriatrics. To curb this issue different approaches like coating, granulation, extrusion, inclusion complexation, ion-exchange resins, etc for taste masking are employed and among them use of lipids have drawn special attention of researchers. Lipids have a lower melting point which is ideal for incorporating drugs in some of these methods like hot-melt extrusion, melt granulation, spray drying/congealing and emulsification. Lipids play a significant role as a barrier to sustain the release of drugs and biocompatible nature of lipids increases their acceptability by the human body. Further, lipids provide vast opportunities of altering pharmacokinetics of the active ingredients by modulating release profiles. In taste sensors, also known as electronic tongue or e-tongue, lipids are used in preparing taste sensing membranes which are subsequently used in preparing taste sensors. Lipid membrane taste sensors have been widely used in assessing taste and palatability of pharmaceutical and food formulations. This review explores applications of lipids in masking the bitter taste in pharmaceutical formulations and significant role of lipids in evaluation of taste and palatability.