MIT-World Peace University (MIT-WPU) is a top educational institute located in Pune, India. It is recognized within&nbsp;UGC under Government of Maharashtra Act No. XXXV 2017.&nbsp;

It is part of the MIT group of institutions (established in 1983) which covers 10+ campuses across India and has more than 50,000+ students enrolled across various disciplines at a given point of time. The institute houses 15 schools ranging from Engineering &amp; Technology, Design, Pharmacy, Commerce, Governance among others. It offers undergraduate, postgraduate and PhD programs among different disciplines.&nbsp;

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MIT World Peace University

Pharmacy

Piperine is a poorly water-soluble drug and its bioavailability is a great barrier for this drug. The objective of current work was to formulate and investigate a self-microemulsifying drug delivery system (SMEDDS) of piperine as well as modification of liquid SMEDDS into the solid SMEDDS. Solubility study of piperine was performed in various excipients. Optimum composition of the microemulsion region was identified by using the pseudo-ternary phase diagram. Liquid SMEDDS formulation was optimized by Box–Behnken statistical design. The optimized liquid SMEDDS formulation showed particle size 22.12 ± 0.88 nm, PDI 0.185 ± 0.03 and transmittance 99.48 ± 0.32%. A methyl thiazolyl tetrazolium (MTT) assay was performed to determine in vitro anticancer efficacy of piperine using KB cell lines. The piperine loaded self-microemulsifying nanoparticles significantly inhibited the growth of carcinoma cells by targeting mitochondria and produced caspases-3 activity. Whereas, this mechanism showed significant role in inhibition of cancer signaling stage. The MTT assay confirmed 98.7% cytotoxicity in cancerous cells. Moreover, PXRD analysis showed the transformation of the crystalline structure of piperine to the amorphous (dissolved) state. In vitro release and ex vivo permeation of liquid and solid-SMEDDS has shown faster drug release as compared to the pure drug. The developed formulation was stable under stability conditions after 3 months of storage. Thus, the studies revealed that SMEDDS has a promising strategy for a poorly water-soluble drug, which benefits to enhance the solubility, dissolution also an anti-proliferative performance of piperine in the oral squamous carcinoma.

World University root node

School of Pharmacy

Journal of Pharmaceutical Investigation

Natural anti-proliferative agent loaded self-microemulsifying nanoparticles for potential therapy in oral squamous carcinoma

Ketoprofen (KP) is a 2-(3-benzolphenyl) propionic acid with anti-inflammatory, analgesic and antipyretic properties. It belongs to BCS Class II drug. It also has a short half-life of 120 minutes. Drugs acidic nature causes gastric irritation which is a major limitation. The present work aims to develop and evaluate solid lipid nanoparticles (SLN) to provide transdermal drug delivery. SLN loaded gel will enhance the solubility of Ketoprofen thereby increasing bioavailability giving controlled drug release. Solid lipid nanoparticles were prepared by solvent injection followed by probe sonication method. Cetyl palmitate was used as lipid and Tween80 as a surfactant. Batches were prepared by varying the concentration of the lipid phase and the surfactant phase. The solid lipid nanoparticles were evaluated for particle size analysis, drug entrapment efficiency, zeta potential and in vitro drug release study. Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD) study were done to study crystallinity behavior.SLN was studied for its anti-inflammatory activity. F4 batch of SLN was incorporated into gel and evaluated for drug content, pH, viscosity, in-vitro diffusion and ex-vivo diffusion study. SLN were successfully prepared. Among the batches F1-F9, F4 batch was selected based upon the size, entrapment efficiency, stability and drug release. The resultant solid lipid nanoparticles showed entrapment efficiency of 78.24%. The solubility was improved by 50 fold. The particle size was 250 nm, PDI was 0.398 and zeta potential -21.98mV. In-vitro drug release of gel from F4 SLN batch showed controlled drug release in 8 hours. Transdermal delivery of SLN retaining its anti-inflammatory activity was successfully developed.

Letters in Applied NanoBioScience

Transdermal delivery of solid lipid nanoparticles of ketoprofen for treatment of arthritis

Self experience

Marathi article on Organ Transplantation

A robust and simplified high-performance liquid chromatography (HPLC) method was developed for the estimation of Pyrazinamide and its related substance. A systematic approach, one of the parts of QbD (quality by design) was used in suitable analytical method development. The HPLC segregation method was carried out with C-18 Column (3.9x300 mm, I. D. 10 μm), a mobile phase of phosphate buffer: Acetonitrile (pH 3.0) 90:10 v/v, detected at 270 nm. Optimization to this method was done by response surface methodology by applying a three-level Box Behnken design with three center points. © 2019 Deuton-X Ltd. All rights reserved.

European Chemical Bulletin

HPLC method development for determination of pyrazinamide and related substance by using Quality by Design (QBD) approach

Cardiotoxicity is a frequent and severe side effect of 5-Fluorouracil (5-FU) chemotherapy, limiting its clinical use despite being one of the most potent anticancer agents. The present study was designed to evaluate the cardioprotective effect of a phenolic acid namely 2-pyrocatechuic acid (2,3 dihyroxybenzoic acid) against 5-FU induced cardiotoxicity in Wistar rats. Exposure to 5-FU at a dose of 20 mg/kg caused significant increase in serum cardiac biomarkers such as lactate dehydrogenase (LDH)), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) activities, cardiac CK-MB index along as well as cTnI levels along with severe histopathological changes in cardiac tissues of rats indicating severe cardiotoxicity. Co-administration of 2- pyrocatechuic acid (2-PCA) with 5-FU at 3, 10, 30 and 100 mg/kg b.w./day for 14 days resulted in an amelioration of altered serum parameters in a dose dependent manner. Moreover, 2-PCA attenuated the cardiac tissue damage produced by 5-FU. The results indicated the potential of 2-PCA as a cardioprotective agent for the prevention and amelioration of 5-FU induced cardiotoxicity.

Latin American Journal of Pharmacy

Protective effect of 2-Pyrocatechuic acid on 5-Fluorouracil induced cardiotoxicity in wistar rats

Background: Hydrochlorothiazide (HCTZ) is a thiazide diuretic and also possesses an anti-hypertensive effect. It is BCS class IV drug with very poor aqueous solubility and permeability. Objective: The objective of the present work was to enhance the solubility and permeability of hydrochlorothiazide via self microemulsifying drug delivery system (SMEDDS) and to optimize gastro-retentive floating delivery for Solid-SMEDD. Method: T Solubility of drug was determined in the oil, surfactant and co-surfactant. Pseudo ternary phase diagram was constructed to identify efficient self emulsifying region. SMEDDS was transformed into a free flowing powder. Non-effervescent floating capsules containing Solid SMEDDS of HCTZ was prepared. Factorial design was used to optimize gastro-retentive delivery of HCTZ using polymer HPMC K4M and HEC HX 250 as independent variables. Results: SMEDDS consists of HCTZ, isopropyl myristate, tween 80 and PEG 400 as drug, oil, surfactant and co-surfactant. 1:1 ratio of the surfactant to co-surfactant gave larger transparent region for microemulsion. Ex-vivo drug release from SMEDDS was higher than plain drug at the end of 4 hrs. Magnesium hydroxide was used to convert SMEDDS to S-SMEDDS. ANOVA indicated that the drug release and swelling index were the most significant factors affecting gastro retentive drug delivery. Optimized batch F5 followed Zero order release model kinetics. Conclusion: The study concluded enhanced solubility of drug by SMEDD. Floating capsules gave controlled drug release in the stomach for longer period of time which reduced the dosing frequency and improved the patient compliance. © 2018 Bentham Science Publishers.

Current Drug Therapy

Development and Optimization of Floating Capsule for Solid Self Microemulsified Drug Delivery of Hydrochlorothiazide

Kukkutandatvakbhasma (Hen Egg shell bhasma) which is known as calcinated Hen egg shell is used in the treatment of leucorrhea in the form of bhasma since ancient times in Ayurveda system of medicines.It is known to have anti-inflammatory, anti-arthritic, rejuvenative for heart and aphrodisiac property.Hence, the objective of present study was to explore its anti-inflammatory activity of Kukkutandatvakbhasma through appropriate animal models.The Kukkutandatvakbhasma of both types of hen egg shell i.e. modern (KKBM-7)and gavran (KKBG-7) was prepared separately using Putapaka method in three steps – Shodhan (purification), Marana and Bhavana. Anti-inflammatory activity of KKBM-7 and KKBG-7 was evaluated using carrageenan inducedpaw edema and Adjuvant-induced chronic arthritis models.Treatment with KKBM-7 (300 and 500 mg/kg) and KKBG-7 (300 and 500 mg/kg) reducedcarrageenan induced rat paw edema volume. Treatment with KKBM-7 (300 and 500 mg/kg) and KKBG-7 (300 and 500 mg/kg) significantly reduced paw volume compared to control group from day 3 till day 21 in Adjuvant-induced chronic arthritismodel.thus, it was concluded that KKBM-7 and KKBG-7 have significant anti-inflammatory activity in acute as well as chronic model of inflammation. © 2018, SILAE (Italo-Latin American Society of Ethnomedicine). All rights reserved.

Pharmacologyonline

Evaluation of anti-inflammatory activity of Kukkutandatvac Bhasma in acute and chronic inflammation models

The bioavailability of therapeutic agents from eye drops is usually limited due to corneal barrier functions and effective eye protective mechanisms. The current study aimed to enhance ocular bioavailability of dorzolamide hydrochloride, a potent antiglaucoma drug by preparing novel ophthalmic drug delivery system like soluble ophthalmic drug inserts (SODI). Various batches of dorzolamide hydrochloride Soluble Ocular Drug Insert were prepared using Polyvinyl Alcohol, Poloxamer 407 as polymer with Propylene Glycol as plasticizer by solvent casting method. The drug inserts were prepared by using 32 factorial designs (version 10). Solvent casting method was used to prepare drug inserts which were further evaluated for various parameters like drug interaction studies, physicochemical characteristics, in vitro release studies, transcorneal permeation study by using excised goat cornea. The optimized batch F2 showed 98.50 ± 0.05% drug release at the end of 6 h and has desired physicochemical properties. The gamma radiation sterilized batch F2 was subjected to sterility test as per Indian Pharmacopeia 2014 and accelerated stability studies as per International Conference on Harmonization stability testing of new drug substances and products guideline, ex vivo and Pharmacodynamic studies. The comparative pharmacokinetic result shows that Dorzolamide Hydrochloride SODI is more effective than the marketed formulation. The promising pharmacokinetic results and possibility of commercial applicability justifies the need of product in market.

Journal of Drug Delivery Science and Technology

Design, optimization and pharmacodynamic comparison of dorzolamide hydrochloride soluble ocular drug insert prepared by using 32 factorial design

Background: Nabumetone is biopharmaceutics classification system (BCS) class II drug, widely used in the treatment of osteoarthritis and rheumatoid arthritis. The most frequently reported adverse reactions for the drug involve disturbance in gastrointestinal tract, diarrhea, dyspepsia and abdominal pain. Microemulgel has advantages of microemulsion for improving solubility for hydrophobic drug. Patent literature had shown that the work for drug has been carried on spray chilling, enteric coated tablet and topical formulation which gave an idea for present research work for the development of transdermal delivery. Objective: The objective of the present research work was to optimize transdermal microemulgel delivery for Nabumetone for the treatment of arthritis. Methods: Oil, surfactant and co-surfactant were selected based on solubility study of the drug. Gelling agents used were Carbopol 934 and HPMC K100M. Optimization was carried out using 32 factorial design. Characterization and evaluation were carried out for microemulsion and microemulsion based gel. Results: Field emission-scanning electron microscopy (FE-SEM) study of the microemulsion revealed globules of 50-200 nm size. Zeta potential -9.50 mV indicated good stability of microemulsion. Globule size measured by dynamic light scattering (zetasizer) was 160nm. Design expert gave optimized batch as F7 which contain 0.2% w/w drug, 4.3% w/w liquid paraffin, 0.71% w/w tween 80, 0.35% w/w propylene glycol, 0.124% w/w Carbopol 934, 0.187% w/w HPMC K100M and 11.68% w/w water. In-vitro diffusion study for F7 batch showed 99.16±2.10 % drug release through egg membrane and 99.15±2.73% drug release in ex-vivo study. Conclusion: Nabumetone microemulgel exhibiting good in-vitro and ex-vivo controlled drug release was optimized.

Recent Patents on Drug Delivery & Formulation

Development of Microemulsion Based Nabumetone Transdermal Delivery for Treatment of Arthritis

Context: Short residence time, poor bioavailability and poor permeability are the major problems for conventional eye drops treatment. Objective: The aim of this article is to develop, optimize and ex vivo–in vivo investigation of brimonidine tartrate in situ gel as compared to marketed eye drops for the treatment of glaucoma. Materials and methods: The effect of independent variables, namely concentrations of polymers, on various dependent variables like viscosity at physiological pH and in vitro drug release were studied by using 32 factorial design. Further the optimized formulation was characterized for ex vivo and in vivo study. Results and discussion: Experimental data demonstrated that optimized in situ gel formulation (F8) showed in vitro–ex vivo sustained release profile with polymer composites carbopol 974P and HPMC K4M. After 5 h of ex vivo transcorneal permeation study, the amount recovered from the corneal surface on the donor chamber 12.40% (124 ug) and the amount collected from the receptor chamber 76.8% (760 ug) of the initial dose 1 mg. The total amount recovered from the permeation experiment was 89.2%. Bioadhesive carbopol 974P and viscosity HPMC K4M composites optimized formulation (F 8) produce greater influence on the duration of drug action and improved intraocular pressure reduction activity as compared to marketed eye drop solution in in vivo study. Conclusion: The developed in situ gelling system as a promising ophthalmic formulation to prolong the drug lowering effect on the intraocular pressure.

Drug Development and Industrial Pharmacy

Formulation and ex vivo–in vivo evaluation of pH-triggered brimonidine tartrate in situ gel for the glaucoma treatment using application of 32 factorial design