Design, optimization and pharmacokinetics of novel prolonged gastroretentive drug delivery system of quetiapine fumarate

Dharmik M. Mehta,Punit B. Parejiya,Hetal K. Patel,Palak J. Trivedi,Disha D. Suthar,Pragna K. Shelat 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.5

Present study attempts to overcome pH-dependent solubility, a limitation for oral delivery of poorly soluble BCS class-II drugs. A pH independent, patient compliant, dual working gastroretentive drug delivery system of model drug quetiapine fumarate (QF) was fabricated by unique combination approach of mucoadhesion and floating. Bilayer tablets comprising floating adhesive layer (FL) and matrix layer (ML) was systematically optimized by applying 32 full factorial experimental designs. Selected variables for FL: Polyox 303WSR (X1FL) and alginate beads (X2FL), and for ML: HPMC K100M (X1ML) and fumaric acid (X2ML) were studied against responses for FL: floating lag time (R1FL), total floating time (R2FL) and adhesion force (R3FL) and for ML: percentage drug released at 2 h—Q2h (R1ML), 8 h—Q8h (R2ML), and 18 h—Q18h (R3ML), respectively. Optimized batch (OP) showed floating lag time (6.5 h), total floating time (14 h), adhesion force (0.82 N) and Q18h ([90 %). Pharmacokinetic study of OP and immediate release market product demonstrated improved bioavailability (*12 % higher AUC0–?) of OP. In a nutshell, developed drug delivery system can be fabricated as a platform for QF and similar BCS class-II drugs with pH dependent solubility.

Development of phenytoin intranasal microemulsion for treatment of epilepsy

Sheetal Porecha Acharya,K. Pundarikakshudu,Pratik Upadhyay,Pragna Shelat,Anita Lalwani 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.4

The objective of the present investigation was to prepare phenytoin microemulsion for intranasal administration by application of experimental design. Phenytoin microemulsion was prepared by water titration method. The concentration of oil (X1), surfactant (X2) and cosurfactant (X3) were selected as independent variables, in a simplex centroid design, from microemulsion region obtained from pseuodoternary phase diagram while the globule size (Y1) and cumulative phenytoin diffused at 60 min (Y2) through sheep nasal mucosa were taken as dependent variables. Mathematical models were generated for the response variables. The validity of the generated equations was established using check point batches. Microemulsion that had a smaller globule size of dispersed phase and high level of % drug diffusion was desirable. The generated mathematical equations were used to identify the desirable zone where all the criteria for the responses were satisfied and an optimum batch was recognized. Ex-vivo study of optimum microemulsion on sheep nasal mucosa shows absence of nasal toxicity. It was found that faster recovery from seizures was obtained in rats treated with intra nasal phenytoin microemulsion in comparison to the rats treated with oral microemulsion and nasal solution. Higher concentration of phenytoin was found in rats treated with intranasal microemulsion in comparison to the rats treated with phenytoin solution administered intraperitoneally. Gamma scintigraphy results also suggested faster availability of drug into brain when microemulsion was administered intranasally.

Physicochemical and toxicological characterization of sucrosebound polynuclear iron oxyhydroxide formulations

Bhavesh S. Barot,Punit B. Parejiya,Pragna K. Shelat,Gaurang B. Shah,Dharmik M. Mehta,Trupti V. Pathak 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.1

Intravenous iron formulations comprising ofiron/iron–oxyhydroxide–carbohydrate complex are anestablished therapy for the treatment of iron deficiency anemia. These preparations should be subjected to exhaustive physicochemical and toxicological studies in order to establish their safety and efficacy. Following VenoferⓇ (innovator iron–sucrose formulation), variousiron sucrose similar have entered into the market with equivalent physicochemical and toxicological profile. This report describes the physicochemical and toxicological studies of a novel iron sucrose injection (IS-Claris). IS-Claris and VenoferⓇ were subjected to various physicochemical studies such as elemental and chemical analysis;X-ray diffraction; particle size and distribution; labile iron detection, Mo¨ssbauer and Raman spectroscopy. The presenceof iron oxides in IS-Claris and VenoferⓇ could be confirmed by the major peaks at 24.65˚ (2θ) and 38.2˚ (2θ). The iron sucrose samples demonstrated similar reduction peaks of Fe(III) to Fe in their respective polarograms. The average diameter of the core of IS-Claris and VenoferⓇ was estimated to be 2.92 ± 0.01 and 2.77 ± 0.63 nm, respectively. The Mo¨ssbauer spectra of IS-Claris and VenoferⓇ showed a doublet with an isomer shift δ = 0.43 ± 0.01 mm/s. Moreover, the other physicochemical specifications of IS-Claris were comparable to VenoferⓇ. The toxicological studies demonstrated that IS-Claris safety profile is equivalent to VenoferⓇ. It could be concluded that IS-Claris could be used as a potential alternative to VenoferⓇ with similar clinical implications.

Release modulation of highly water soluble drug using solid dispersion: impact of dispersion and its compressed unit

Punit B. Parejiya,Bhavesh S. Barot,Hetal K. Patel,Dharmik M. Mehta,Pragna K. Shelat,Arunkumar Shukla 한국약제학회 2014 Journal of Pharmaceutical Investigation Vol.44 No.3

In present day, availability of various carriers,innovative techniques of production and plenty of solventssupport the growth of solid dispersion (SD) technology inpharmaceutical industries to overcome many issues. Thepresent study was aimed to develop SD based sustainedrelease system of Milnacipran HCl (MH). The SD containingethyl cellulose, Eudragit RLPO and Eudragit RSPOat drug–polymer ratios of 1:1, 1:2, and 1:3 were developedusing solvent evaporation technique and different waxes atratio of 1:1, 1:1.25, 1:1.5 and 1:1.75 with drug weredeveloped by melting method. The physicochemicalproperties of SD were evaluated using Fourier transforminfrared spectroscopy (FTIR), differential scanning calorimetry(DSC) and X-ray diffraction (XRD). The desiredSD batch was further compressed into tablet unit to achievepredetermined once a day drug release. Tablets preparedwere evaluated for physicochemical parameters, in vitrodrug release, drug release kinetics and scanning electronmicroscopy. Out of selected carriers, bees wax had shownmaximum release retardation. The results of FTIR, DSCand XRD studies exhibited poor interaction amongst MH–bees wax and retention of crystalline state of MH in SDsystem. The presence of Benecel (HPMC K 200 M;75 mg) in tablets comprising SD (1:1.25, MH:bees wax)revealed remarkable drug release extension and it wasconsidered an optimal. The later was submitted to shortterm stability study and its results indicated the stablecharacteristic of system. Drug release from optimizedformulation fitted well into Higuchi model with anomalousdiffusion. The compressed unit of SD system of highlywater soluble drug can be successful single day regimen.

Quick dissolving films of nebivolol hydrochloride: formulation and optimization by a simplex lattice design

Punit B. Parejiya,Rakshit C. Patel,Dharmik M. Mehta,Pragna K. Shelat,Bhavesh S. Barot 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.4

Present study aims at formulation and development of quick dissolving film of nebivolol hydrochloride applying simple lattice experimental design using three hetero polymers hydroxypropyl methylcellulose, pullulan and polyvinyl pyrrolidone. Films were prepared using solvent casting technique and optimized formulation was derived by desirability function. Regression equations and contour plots were executed to narrate dependent variables,i.e. percentage drug release in 30 s (Y30), tensile strength,elastic modulus, percentage elongation and load at yield, to independent variables. Results of the experimental design revealed that the independent factors hydroxypropyl methylcellulose and pullulan significantly influenced the mechanical properties and percentage drug release from the film which was ultimately reflect in the formulation of optimized batch. The high % drug release of the film in simulated saliva and simulated gastric fluid indicated that it can be successfully used in drug delivery systems for drugs with high first-pass metabolism.