Lyophilized mixed micelles of exemestane: A novel paradigm to improve its absorption and anticancer activity.

The objective of the present investigation was to prepare and optimize lyophilized mixed micelles (Lyp-EXE-MMs) of exemestane (EXE) with improved solubility, bioavailability, in vivo anticancer activity, and physical stability, by using various cryoprotectants. The prepared lyophilized mixed micelles were characterized by various techniques, including dynamic light scattering, zeta potential, powdered X-ray diffraction, differential scanning calorimetry (DSC), nuclear magnetic resonance ( H NMR), transmission electron microscopy (TEM), and so on. Thereafter, the lyophilized micelles were evaluated for ex vivo permeation, in vitro drug release and gene/protein expression (RT-PCR and Western blot analysis) in MCF-7 breast cancer cells.

Convolutions in the rendition of nose to brain therapeutics from bench to bedside: Feats & fallacies.

Brain, a subtle organ of multifarious nature presents plethora of physiological, metabolic and bio-chemical convolutions that impede the delivery of biomolecules and thereby resulting in truncated therapeutic outcome in pathological conditions of central nervous system (CNS). The absolute bottleneck in the therapeutic management of such devastating CNS ailments is the BBB. Another pitfall is the lack of efficient technological platforms (due to high cost and low approval rates) as well as limited clinical trials (due to failures of neuro‑leads in late-stage pipelines) for CNS disorders which has become a literal brain drain with poorest success rates compared to other therapeutic areas, owing to time consuming processes, tremendous convolutions and conceivable adverse effects.

Polymeric Precipitation Inhibitor Based Supersaturable Self-microemulsifying Drug Delivery System of Canagliflozin: Optimization and Evaluation.

Background: The present investigation attempts to optimize Supersaturable lipid based formulation (SS SMEDDS) of Biopharmaceutical Classification System (BCS) class IV drug canagliflozin (CFZ) and evaluating the oral bioavailability of the formulation.

Methods: Preliminary screening revealed Poloxamer 188 to most effectively inhibit precipitation of CFZ after dispersion during in vitro supersaturation studies. Box Behnken Design was employed for designing different formulations, and various statistical analyses were done to select an appropriate mathematical model.

Evaluation of Bio-Mechanistic Behavior of Liquid Self-Microemulsifying Drug Delivery System in Biorelevant Media.

In vitro, An in vitro

Engineered Site-specific Vesicular Systems for Colonic Delivery: Trends and Implications.

Steering drug-loaded, site-specific, coated lipid vesicles to the target receptor sites have the potential of plummeting adverse effects and improving the pharmacological response in diverse pathologies of the large bowel, especially the colon. Colonic delivery via oral route has its own challenges, often governed by several glitches such as drug degradation or absorption in the upper GIT, instability of proteins/peptides due to high molecular weight, and peptidase activity in the stomach. Consequently, colon-specific coated liposomal systems (CSLS) offer a potential alternate for not only site-specificity, but protection from proteolytic activity, and prolonged residence time for greater systemic bioavailability.

Enhanced oral bioavailability and anti-diabetic activity of canagliflozin through a spray dried lipid based oral delivery: a novel paradigm.

Aim: Canagliflozin (CFZ), a novel SGLT II antagonist, exhibits erratic absorption after oral administration. The current study entails development and evaluation of spray dried lipid based formulation (solid SMEDDS) for enhancing oral bioavailability and anti-diabetic activity of CFZ.

Methods: Solid SMEDDS developed through spray drying containing Neusilin US2 as an adsorbent.

Bio-Inspired Strategies against Diabetes and Associated Complications: A Review.

Bio-molecules are the most important target to be considered while designing any drug delivery system. The logic lies in using such bio-sensing or bio-mimicking systems in their formulations that can mimic the active site of those receptors to which the drug is going to bind. Polymers mimicking the active site of target enzymes are regarded as bio-inspired polymers and can be used to ameliorate many diseased conditions.

Polymeric precipitation inhibitor as an effective trigger to convert supersaturated into supersaturable state .

The supersaturated state of the drug is thermodynamically unstable resulting in a delayed response and reduced efficacy. The use of polymeric precipitation inhibitor (PPI) has been demonstrated as an effective trigger for the conversion of supersaturated state to supersaturable state for improving solubilization, thermodynamic maintenance of drug concentration and oral absorption of poorly water-soluble compounds. PPI retards drug precipitation and provides a kinetically stabilized supersaturation state for an extended period in gastric and intestinal fluids.

Self-microemulsifying Drug Delivery System for Problematic Molecules: An Update.

Background: The poor bioavailability of a problematic molecule is predominantly due to its high lipophilicity, low solubility in gastric fluids and/or high fist pass metabolism. Self microemulsifying drug delivery system (SMEDDS), a lipidic type IV nano-formulation has been of interest in the field of pharmaceutical research due to its potential for tailoring the physicochemical properties of pharmaceutical molecules.

Methods: This review provides insights on various recent innovations and reports from the past seven years (2012-2019) of self-emulsifying formulations for the delivery of various types of poorly soluble drugs, phytoconstituents and high molecular peptides and gives exhaustive details of the outcome of the endeavors in this field.

Role of Porous Carriers in the Biopharmaceutical Performance of Solid SMEDDS of Canagliflozin.

Objective: The aim of the present investigation entails the development of solid SMEDDS for improving the oral bioavailability of canagliflozin using porous carriers. The previous patent (WO2017046730A1) was based on enhanced solubility of canagliflozin through co-crystal formation.

Methods: Preconcentrates were prepared by employing Lauroglycol (80 mg), Tween 80 (300 mg) and Transcutol P (120 mg) and successfully adsorbed onto various hydrophilic and hydrophobic carriers.

Improved pharmacokinetic and pharmacodynamic attributes of artemether-lumefantrine-loaded solid SMEDDS for oral administration.

Objectives: To evaluate the in-vivo efficacy of solid SMEDDS containing combination of artemether and lumefantrine.

Methods: Formulation development of solid SMEDDS containing combination of artemether and lumefantrine was carried out using spray drying technique. These S-SMEDDS were evaluated for reduction in parasitemia and mortality as well as subacute toxicity in mice.

Antimalarial solid self-emulsifying system for oral use: in vitro investigation.

Aim: The low aqueous solubility of artemether and lumefantrine makes them less bioavailable. It is expected that by formulating self-microemulsifying drug-delivery systems (SMEDDS), their aqueous solubility and absorption will thus be enhanced. Results & methodology: Optimized liquid SMEDDS containing artemether and lumefantrine was adsorbed on Neusilin US2 employing spray drying technique to convert it into solid SMEDDS.

Microemulsion Transdermal Formulation for Simultaneous Delivery of Valsartan and Nifedipine: Formulation by Design.

The objective of the study was to optimize the proportion of different components for formulating oil in water microemulsion formulation meant for simultaneous transdermal delivery of two poorly soluble antihypertensive drugs. Surface response methodology of Box-Behnken design was utilized to evaluate the effect of two oils (Captex 500 - x1 and Capmul MCM - x2) and surfactant (Acrysol EL135 - x3) on response y1 (particle size), y2 (solubility of valsartan), and y3 (solubility of nifedipine). The important factors which significantly affected the responses were identified and validated using ANOVA.

Understanding pharmaceutical polymorphic transformations II: crystallization variables and influence on dosage forms.

Excipients or formulation variables have often been exploited to improve stability, modify release, or improve physicochemical properties of dosage forms. In pharmaceutical field, it is generally expected that excipients work at macromolecular level where they might influence the crystal structure of a solid. These polymers/colloidal particles may modify the rate and direction of crystal growth.

Understanding pharmaceutical polymorphic transformations I: influence of process variables and storage conditions.

The active pharmaceutical ingredient (API) of a dosage form is affected by number of mechanical and environmental factors which have a tendency to alter its crystalline state. Polymorphic transitions have been observed to occur during various unit operations like granulation, milling and compression. Forces of pressure, shear and temperature have an ability to induce alterations in crystal habit.

Anti-cancer, pharmacokinetic and biodistribution studies of cremophor el free alternative paclitaxel formulation.

Purpose: The aim of the present investigation is to determine the in vivo potential of previously developed and optimized Cremophor EL free paclitaxel (CF-PTX) formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate. CF-PTX was found to have drug loading of 6 mg/ml similar to Cremophor EL based marketed paclitaxel formulation. In the present study, intracellular uptake, repeated dose 28 days sub-acute toxicity, anti-cancer activity, biodistribution and pharmacokinetic studies were conducted to determine in vivo performance of CF-PTX formulation in comparison to marketed paclitaxel formulation.

A critical appraisal of microemulsions for drug delivery: part II.

Microemulsions are thermodynamically stable, optically transparent isotropic solutions of oil and water successfully formulated by using a combination of suitable surfactant and cosurfactant. The solubilization power of microemulsions for lipophilic, hydrophilic and amphiphilic solutes form a viable approach for enhancing the bioavailability of hydrophobic drugs and percutaneous permeation of poorly permeable drugs, mainly due to the large area per volume ratio available for mass transfer. Microemulsions have emerged as novel vehicles for drug delivery due to their versatile applications.

A critical appraisal of microemulsions for drug delivery: part I.

Microemulsions (MEs) are thermodynamically stable, optically transparent isotropic solutions of oil and water successfully formulated by using a combination of suitable surfactant and cosurfactant. While the selection of oil is based primarily on the solubility of drug in it, surfactant is generally selected on the basis of its hydrophilic-lipophilic balance value. MEs are characterized by ultra-low interfacial tension between the immiscible phases and offer the advantage of spontaneous formation, thermodynamic stability and ease of manufacture.

Sulfation of Aegle marmelos gum: synthesis, physico-chemical and functional characterization.

The present investigation was aimed at optimizing the conditions for preparing sulfated derivative of gum obtained from partially ripe fruits of Aegle marmelos. Elemental analysis, FTIR-ATR and NMR studies confirmed successful sulfation. The ratio of chlorosulfonic acid to pyridine exerted maximum influence on the degree of substitution followed by reaction temperature and reaction time.

Tight junctions in skin: new perspectives.

Tight junctions (TJs) are intercellular contacts that seal the space between the individual cells of an epithelial sheet or stratifying epithelia, such as the epidermis, so that they can collectively separate tissue compartments. Intercellular junctions, such as adherens and TJs, play a crucial role in the formation and maintenance of epithelial and endothelial barriers. A variety of components including claudins, occludin, tricellulin, zonula occluden proteins and junctional adhesion molecules have been identified in complex localization patterns in mammalian epidermis.

Optimization of an aqueous tablet-coating process containing carboxymethylated Cassia fistula gum.

The present investigation was aimed at developing and optimizing a simple aqueous tablet-coating formulation and its process. 5-Fluorouracil (5-FU) was used to ascertain the relative lipophilic/hydrophilic behavior of the coating system. Optimization was performed by evaluating the adhesive force strength and cohesive force strength of the tablet coat using a texture analyzer.

Hot melt granulation: a facile approach for monolithic osmotic release tablets.

The aim of this work was to develop and evaluate an extended release matrix tablet of glipizide (GP), an oral hypoglycemic agent. Matrices of GP were prepared using microcrystalline cellulose Avicel(™) PH 112, sodium chloride (SC) and polyethylene glycol 6000 (PEG). The content of Kollidon SR (KR), hydroxypropyl methylcellulose K4M premium CR grade (HM) and polyethylene oxide WSR 303 (PO) and/or magnesium hydroxide (MH) was varied in different formulations.

Fabrication and optimization of fast disintegrating tablets employing interpolymeric chitosan-alginate complex and chitin as novel superdisintegrants.

The objective of the present work was to optimize the formulation of fast disintegrating tablets (FDTs) of ondansetron HCl containing novel superdisintegrants, possessing sufficient mechanical strength and disintegration time comparable to those containing crospovidone or croscarmellose sodium. The FDTs were formulated using a novel superdisintegrant (chitosan-alginate (1:1) interpolymer complex and chitin) to achieve a sweet tasting disintegrating system. The results revealed that chitin (5-20%) increased the porosity and decreased the DT of tablets.