Priti Girotra

Supercritical fluid technology: a promising approach in pharmaceutical research

Supercritical fluids possess the unique properties of behaving like liquids and gases, above their critical point. Supercritical fluid technology has recently emerged as a green and novel technique for various processes such as solubility enhancement of poorly soluble drugs, plasticization of polymers, surface modification, nanosizing and nanocrystal modification, and chromatographic extraction. Research interest in this area has been fuelled because of the numerous advantages that the technology offers over the conventional methods. This work aims to review the merits, demerits, and various processes such as rapid expansion of supercritical solutions (RESS), particles from gas saturated solutions (PGSS), gas antisolvent process (GAS), supercritical antisolvent process (SAS) and polymerization induced phase separation (PIPS), that have enabled this technology to considerably raise the interest of researchers over the past two decades. An insight has been given into the numerous applications of this technology in pharmaceutical industry and the future challenges which must be appropriately dealt with to make it effective on a commercial scale.

Development of zolmitriptan loaded PLGA/poloxamer nanoparticles for migraine using quality by design approach.

The purpose of this investigation was to develop Poly (D,L Lactide-co-Glycolide) (PLGA)/poloxamer nanoparticles (NPs) of the hydrophilic drug Zolmitriptan using quality-by-design approach for brain targeting. Randomized 2(4) full factorial design was employed to achieve the critical quality attributes of minimized particle size and maximized encapsulation efficiency. The PLGA/poloxamer NPs were fabricated using modified double emulsion solvent diffusion technique and particle size varied from 165.4-245.4 nm, encapsulation efficiency was in the range of 48.96-95.97% and percent cumulative drug release varied from 43.32 to 100%. The optimized nanoparticles were characterized by FTIR spectroscopy and powder X-ray diffraction technique which indicated the loading of drug in NPs without any chemical interactions between drug and the excipients. The uniform and spherical shape of the particles was affirmed from TEM analysis. The in-vivo studies for determination of brain uptake potential demonstrated a 14.13 fold increase in drug delivered to brain from the NPs as compared to the free drug. The pharmacodynamic studies involving Swiss albino mice further confirmed successful delivery of drug to brain circumventing the blood brain barrier, through significantly enhanced anti-migraine potential. This investigation thus presents the suitability of zolmitriptan loaded PLGA/poloxamer NPs in brain targeting for the efficient treatment of migraine.

Targeting silymarin for improved hepatoprotective activity through chitosan nanoparticles

Introduction: Silymarin is one of the best known hepatoprotective drugs, which is obtained from the seeds of Silybum marianum L., Family: Asteraceae or Compositae. The plant has traditionally been used for centuries as a natural remedy for liver and biliary tract diseases. The aim of the present investigation was to enhance the hepatoprotective activity of silymarin by incorporating it in chitosan (Ch) nanoparticles (NPs) for passive targeted delivery, thereby prolonging its retention time. Materials and Methods: Silymarin loaded NPs were prepared by ionic gelation technique, which were then optimized using a central composite design in order to minimize the particle size and maximize the drug entrapment efficiency. The optimized formulation was evaluated for in vitro drug release study and in vitro study on Swiss Albino mice using carbon tetrachloride (CCL4) induced hepatotoxicity model. Results: In vitro dissolution studies illustrated sustained, zero order drug release from optimized formulation; also its therapeutic potential was amplified during in vitro studies on Swiss Albino mice using CCL4 induced hepatotoxicity model. Conclusion: The results suggested that NPs of silymarin could successfully enhance its hepatoprotective effect by passive targeting and sustained release.

Disentangling the Intricacies of Migraine: A Review

The etiology of migraine, a neurological disorder, has still not been clearly established, although it may be categorized as a headache disorder with specific characteristics such as focal neurological symptoms preceding or accompanying the headache. Many researchers have suggested genetic predisposition as one of the underlying causes of migraine. An insight into the various pathophysiological mechanisms such as the role of cortical spreading depression, abnormal brain stem activity, trigeminal nerves, calcitonin gene related peptide, nitric oxide and serotonin receptors in the development of migraine, has been conferred in the present article. The accurate diagnosis of migraine and identification of its type is a prerequisite for appropriate therapy. Ample opportunity still exists for the improvement in the safety, efficacy and tolerance capacity of the currently available antimigraine medications, through the design and development of targeted drug delivery system. In the present review, an attempt has been made to highlight all the underlying pathophysiological mechanisms of migraine, its diagnosis, treatment and therapeutic area to be explored including mitigation of biochemical pathways and gene therapy.

Identification of multi-targeted anti-migraine potential of nystatin and development of its brain targeted chitosan nanoformulation.

The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (β2 adrenoceptor, Dopamine D3, 5HT1B, TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database. Molecular docking, performed on the obtained hit compounds from virtual screening, indicated nystatin to be the only active lead against the receptors iGluR5 kainate receptor (1VSO), CGRP (3N7R), β2 adrenoceptor (3NYA) and Dopamine D3 (3PBL) with a high binding energy of -11.1, -10.9, -10.2 and -12kcal/mole respectively. The anti-migraine activity of nystatin was then adjudged by fabricating its brain targeted chitosan nanoparticles. Its brain targeting efficacy, analyzed qualitatively by confocal laser scanning microscopy, demonstrated a significant amount of drug reaching the brain. The pharmacodynamic models on Swiss male albino mice revealed significant anti-migraine activity of the nanoformulation. The present study reports for the first time the therapeutic potential of nystatin in migraine management, hence opening avenues for its future exploration.