Formulation development of directly compressible co-processed excipient for sustained release of tramadol hydrochloride

Hetal Patel,Aakash Ghayal,Ashish Mishra,Shailesh Shah 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.1

The objective of present investigation was toprepare and evaluate directly compressible co-processedexcipient for sustained release tablets. Tramadol hydrochloridewas selected as a model drug. Percentage ofglyceryl monostearate, proportion of dicalcium phosphatedihydrate with respect to glyceryl monostearate and concentrationof polyvinyl pyrrolidone (PVP K30) wereselected as independent variables in 3³ Box–Behnkendesign. Percentage drug release at given time (Q3, Q6, Q12)and Carr’s index were selected as dependent variables. Glyceryl monostearate and dicalcium phosphate dihydrateblend was granulated with PVP K30 and passed through 30mesh sieve to prepare co-processed excipient. This wasevaluated for percentage fines, Carr’s index, particle sizedistribution and granular friability index. Drug was mixedwith co-processed excipient and sustained release tabletswere prepared and evaluated. Regression analysis wascarried out to evolve full and refined models. Contour plotswere presented for graphical expression of the results. Themechanism of drug release from all batches followed Fickiandiffusion. Optimized batch was found to be stable for3 months at accelerated conditions (40 ˚C/75 % RH). Itcan be concluded that multifunctional directly compressibleco-processed excipient of glyceryl monostearate anddicalcium phosphate dihydrate can successfully be used tosustain the release of highly water soluble drugs.

Novel time and site specific ‘‘tablets in capsule’’ system for nocturnal asthma treatment

Sonia Pandey,Preety Mehta,Hetal Patel,Ritesh Shah,Arti Gupta,Ashish Mishra 한국약제학회 2014 Journal of Pharmaceutical Investigation Vol.44 No.5

The objective of present work was to develop a‘‘tablets in capsule’’ system for facilitating both immediateand pulsatile drug deliveries of theophylline to mimic thecircadian rhythm of nocturnal asthma. The system comprisedof capsule filled with two tablets, first pulse andsecond pulse tablet prepared by wet granulation method. First pulse tablet was not coated and was responsible forproviding loading dose whereas; second pulse tablet wascoated with Eudragit L100 and Eudragit S100 to releasedrug in colon after specific lag time. Two independentvariables, amount of polymers and coating thickness, wereoptimized by 32 full factorial design. The optimum formulationconsisted of Eudragit L100: Eudragit S100 in1:1.5 ratio and coating thickness of 20 % (w/w). In vitrodrug release of ‘‘tablets in capsule’’ system in three differentmedia (pH 1.2, pH 6.8, and pH 7.4) revealedimmediate and pulsatile release patterns.

Development and characterization of microemulsion based topical gel of essential oil of clove (Syzygium aromaticum) for superficial fungal infections

Gandhi Jeet,Suthar Disha,Patel Hetal,Shelat Pragna,Parejiya Punit 경희대학교 융합한의과학연구소 2021 Oriental Pharmacy and Experimental Medicine Vol.21 No.3

A widespread of superficial fungal infections deals with concerns related to current therapeutic regimen such as drug resistance and adverse events associated with the same which leads exploration of natural oils as an antifungal agent. The aim of present work is to the development of clove oil loaded microemulsion based gel for treatment of superficial fungal infections. The microemulsion based gel was prepared by phase titration method and optimized using D-optimal design considering globule size, drug permeation and drug retention on skin as critical quality attributes. The MIC and zone of inhibition of clove oil was found to be 2.2 mg/ml and 38 mm respectively. A pale to yellowish transparent microemulsion had a globule size, zeta-potential and PDI of 14.41 nm, 0.73 and 0.0113 respectively indicating a stable microemulsion. A clove oil loaded microemulsion based gel (CLMBG) with a pH of 6.27 and viscosity of 12.87 m.pas/sec exhibited a comparable texture profile to marketed preparation. The drug release of the CLMBG with a drug content of 102.6 ± 4% in acetate buffer pH 5.5 was 98.5 ± 0.35% ensuring complete drug release from the formulation. Ex-vivo drug permeation study and skin irritation study dictated the retention of drug at site of action and the formulation to be non-irritant. The antifungal study proved the formulation to have similar efficacy as the marketed product (clobet gel). The stability study indicated the product to be safe, efficacious and stable formulation. From the above results, it can be derived that clove oil loaded microemulsion based gel can be a promising alternative to current antifungal regimens.

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.

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.