Development of an Correlation for Sitagliptin and Metformin Prolonged-release Tablet Formulations.

Objectives: The objective of this study was to establish and validate an correlation (IVIVC). To investigate the safety of a fixed-dose combination (FDC) versus the reference formulations (Januvia 100 mg Filmtabletten co-administered with Glucophage SR 1000 mg prolonged-release tablets), a bioequivalence study was conducted in the fasted and fed states, and the data generated were used to establish the correlation.

Materials And Methods: The formulations used in the bioequivalence study were a FDC (sitagliptin hydrochloride equivalent to 100 mg of sitagliptin and metformin hydrochloride 1000 mg prolonged release) and Januvia 100 mg co-administered with Glucophage SR 1000 mg.

Development and Optimization of a Novel Prolonged Release Formulation to Resist Alcohol-Induced Dose Dumping.

Alcohol-induced dose dumping is a serious concern for the orally administered prolonged release dosage forms. The study was designed to optimize the independent variables, propylene glycol alginate (PGA), Eudragit RS PO (ERS) and coating in mucoadhesive quetiapine prolonged release tablets 200 mg required for preventing the alcohol-induced dose dumping. Optimal design based on response surface methodology was employed for the optimization of the composition.

Oral transmucosal delivery of domperidone from immediate release films produced via hot-melt extrusion technology.

The objective of the study was to prepare and characterize the domperidone (DOM) hot-melt extruded (HME) buccal films by both in vitro and in vivo techniques. The HME film formulations contained PEO N10 and/or its combination with HPMC E5 LV or Eudragit RL100 as polymeric carriers, and PEG3350 as a plasticizer. The blends were co-processed at a screw speed of 50 rpm with the barrel temperatures ranging from 120-160°C utilizing a bench top co-rotating twin-screw hot-melt extruder using a transverse-slit die.

Effect of pomegranate juice on intestinal transport and pharmacokinetics of nitrendipine in rats.

Pomegranate juice (PJ) is known to be a potent inhibitor of human cytochromes (CYP), particularly CYP2C9 and CYP3A4. The purpose of this study was to investigate the effect of oral PJ on the pharmacokinetics of nitrendipine (10 mg/kg) in rats. The effect of PJ was also investigated on the absorption kinetics of nitrendipine in rats using a single-pass intestinal perfusion model.

Transmucosal delivery of domperidone from bilayered buccal patches: in vitro, ex vivo and in vivo characterization.

Bilayered mucoadhesive buccal patches for systemic administration of domperidone (DOM), a dopamine-receptor (D(2)) antagonist, were developed using hydroxy propyl methyl cellulose and PVPK30 as a primary layer and Eudragit RLPO and PEO as a secondary layer. Ex vivo drug permeation through porcine buccal membrane was performed. Bilayered buccal patches were developed by solvent casting technique and evaluated for in vitro drug release, moisture absorption, mechanical properties, surface pH, in vitro bioadhesion, in vivo residence time and ex vivo permeation of DOM through porcine buccal membrane from a bilayered buccal patch.

P-Glycoprotein- and cytochrome P-450-mediated herbal drug interactions.

P-Glycoprotein (P-gp), the most extensively studied ATP-binding cassette transporter, functions as a biological barrier by extruding toxic substances and xenobiotics out of cells. Drug efflux pumps such as P-gp play a functional role in determining the pharmacokinetics of drugs administered by oral and parenteral routes. Determining the activity of drug efflux transport proteins has important implications in the identification of substrates and/or inhibitors.

Development of bioadhesive buccal tablets for felodipine and pioglitazone in combined dosage form: in vitro, ex vivo, and in vivo characterization.

The purpose of the present research was to develop bioadhesive buccal tablets for Felodipine (FDP) and Pioglitazone (PIO), low bioavailability drugs, in a combined dosage form for the management of diabetes and hypertension. Buccal tablets were prepared by direct compression method using bioadhesive polymers hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, and carbopol, alone or in combination of two polymers, and were evaluated for physicochemical properties, swelling index, in vitro bioadhesion, in vivo residence time, in vitro drug release, and ex vivo permeation through porcine buccal membrane. Formulation (PF6) showed peak detachment force (3.

Role of cyclodextrin complexation in felodipine-sustained release matrix tablets intended for oral transmucosal delivery: in vitro and ex vivo characterization.

The objective of the present research was two-fold: To characterize the produced inclusion complex of felodipine (FDP)-hydroxypropyl-β-cyclodextrin (HPβCD) utilizing lyophilization, and to develop and characterize a complexed sustained-release polymeric matrix tablets intended for buccal delivery. The phase-solubility diagram suggested an A(L) type system with 1:1 stoichiometry. Solid complexes prepared by physical mixing and lyophilization were characterized by thermal and non-thermal analytical techniques to corroborate the fact of complex formation.

Development of a high-performance liquid chromatography method for simultaneous determination of pioglitazone and felodipine in pig serum: application to pharmacokinetic study.

A simple and sensitive high-performance liquid chromatographic method was developed and validated for simultaneous estimation of pioglitazone and felodipine in pig serum. The present method consists of protein precipitation, extraction of analytes from pig serum into dichloromethane and separation using reversed-phase C(18) column. Nitrendipine was used as an internal standard and the eluent was monitored by UV detector at 240 nm.

Transdermal therapeutic system of isradipine: effect of hydrophilic and hydrophobic matrix on in vitro and ex vivo characteristics.

Isradipine (ISDP) is an effective calcium channel blocker used in the treatment of hypertension. It undergoes extensive first pass metabolism and bioavailability through the oral route is only about 15 to 24%. Hence we attempted to develop a matrix type controlled transdermal drug delivery system for ISDP.

Enhanced bioavailability of buspirone from reservoir-based transdermal therapeutic system, optimization of formulation employing Box-Behnken statistical design.

The purpose of the present study was to develop and optimize reservoir-based transdermal therapeutic system (TTS) for buspirone (BUSP), a low bioavailable drug. A three-factor, three-level Box-Behnken design was employed to optimize the TTS. Hydroxypropyl methylcellulose, D: -limonene and propylene glycol were varied as independent variables; cumulative amount permeated across rat abdominal skin in 24 h, flux and lag time were selected as dependent variables.

High-performance liquid chromatography determination of carvedilol in pig serum.

A simple and sensitive analytical method for quantification of carvedilol in pig serum was developed and validated. Carvedilol and internal standard (IS) were extracted into n-hexane-dichloromethane solvent system and separated using an isocratic mobile phase on a Phenomenex C(18) column. The eluent was monitored by spectroflourimetric detector at a flow rate of 1.

Development of novel bioadhesive buccal formulation of diltiazem: in vitro and in vivo characterization.

The aim of the investigation was to develop and evaluate buccoadhesive tablets of diltiazem hydrochloride (DZH) using hydroxypropyl methyl cellulose (HPMC) K4M and Carbopol 934 as mucoadhesive polymers. Formulations A1, A2, A3, A4, and B1, B2, and B3, were composed of HPMC K4M and Carbopol 934 at ratios of 1:2, 1:3, 1:4, 1:5, and 1:1, 1:2, 1:3, respectively. The developed formulations were evaluated for physicochemical, in vitro drug release, in vitro adhesion and in vivo studies in healthy human volunteers.

Enhanced bioavailability of lacidipine via microemulsion based transdermal gels: formulation optimization, ex vivo and in vivo characterization.

The purpose of the present study was to develop and optimize the microemulsion based transdermal therapeutic system for lacidipine (LCDP), a poorly water soluble and low bioavailable drug. The pseudo-ternary phase diagrams were developed for various microemulsion formulations composed of isopropyl myristate, Tween 80 and Labrasol. The microemulsion was optimized using a three-factor, three-level Box-Behnken design, the independent variables selected were isopropyl myristate, surfactant mixture (Tween 80 and Labrasol) and water; dependent variables (responses) were cumulative amount permeated across rat abdominal skin in 24h (Q(24); Y(1)), flux (Y(2)), and lag time (Y(3)).

Matrix-type transdermal drug delivery system of trandolapril: in vitro and ex vivo characterization.

The purpose of the investigation was to develop and evaluate matrix-type transdermal drug delivery systems (TDDSs) of trandolapril. Matrix-type TDDSs of trandolapril were prepared by solvent evaporation technique. Eight formulations (composed of Eudragit RL 100 and Hydroxypropyl methyl cellulose 15 cps at a ratios of 2:8, 4:6, 6:4, 8:2 in formulations A1, A2, A3, A4; and Eudragit RS 100 and Hydroxypropyl methyl cellulose 15 cps in the same ratios in formulations B1, B2, B3, B4, respectively) were prepared.

Development of carvedilol transdermal patches: evaluation of physicochemical, ex vivo and mechanical properties.

Monolithic matrix-type transdermal drug delivery systems for carvedilol were prepared using a film casting technique involving hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), Eudragit RS 100 (ERS 100), and Eudragit RL 100 (ERL 100) as matrix-forming polymers. The prepared transdermal drug delivery systems were extensively evaluated for in vitro release, ex vivo permeation through rat abdominal skin, moisture absorption, moisture content, water vapor transmission, stability, and mechanical properties. Formulations F2, F3, and F5 were composed of a 4:1 ratio of HPMC, ERS 100; HPMC, HPC; and HPMC, ERL 100, respectively, whereas F4, F6, and F7 were composed of 3:0.

Development of ultra fast liquid chromatographic method for simultaneous determination of nitrendipine and carvone in skin diffusate samples.

A simple and sensitive reverse phase ultra fast liquid chromatographic (UFLC) method for simultaneous determination of nitrendipine and carvone in skin diffusate samples and microemulsions was developed and validated. The separation was achieved using a gradient mobile phase, on an Onyx column. The eluents were monitored by photodiode array detection.

Development of high performance liquid chromatography method for buspirone in rabbit serum: Application to pharmacokinetic study.

A simple and sensitive high performance liquid chromatographic (HPLC) method for quantification of buspirone (BUSP) in rabbit serum was developed and validated. BUSP and internal standard (IS), diltiazem hydrochloride were extracted into dichloromethane and separated using an isocratic mobile phase, on a Kromasil C(8) column. The eluent was monitored by UV detector at 235 nm and at a flow rate of 1.

Iontophoretic delivery of lisinopril: Optimization of process variables by Box-Behnken statistical design.

The objective of the investigation was to optimize the iontophoresis process parameters of lisinopril (LSP) by 3 x 3 factorial design, Box-Behnken statistical design. LSP is an ideal candidate for iontophoretic delivery to avoid the incomplete absorption problem associated after its oral administration. Independent variables selected were current (X(1)), salt (sodium chloride) concentration (X(2)) and medium/pH (X(3)).

Optimization of hydrogels for transdermal delivery of lisinopril by Box-Behnken statistical design.

The aim of this study was to investigate the combined influence of three independent variables on the permeation kinetics of lisinopril from hydrogels for transdermal delivery. A three-factor, three-level Box-Behnken design was used to optimize the independent variables, Carbopol 971 P (X(1)), menthol (X(2)), and propylene glycol (X(3)). Fifteen batches were prepared and evaluated for responses as dependent variables.

In vitro permeation of carvedilol through porcine skin: effect of vehicles and penetration enhancers.

This investigation studied the effect of vehicles on the in vitro permeation of carvedilol from saturated solutions across porcine skin and selected appropriate penetration enhancers. Labrasol, Transcutol, polyethylene glycol 400, propylene glycol, ethanol, oleic acid, isopropyl myristate, and phosphate buffered saline (pH 7.4) containing 40% v/v polyethylene glycol 400 as control, were used as vehicles; limonene, carvone, camphor, menthol, Transcutol, and Labrasol at 5% w/v concentrations were used as penetration enhancers.

Development of high performance liquid chromatography method for lacidipine in rabbit serum: application to pharmacokinetic study.

A simple and sensitive high performance liquid chromatographic (HPLC) method for quantification of lacidipine (LCDP) in rabbit serum was developed and validated. LCDP and internal standard (IS), felodipine were extracted into n-hexane and dichloromethane (70:30) solvent system and separated using an isocratic mobile phase, on an Inertsil C18 column. The effluent was monitored by UV detector at 240 nm and at a flow rate of 1.

Transbuccal delivery of chlorpheniramine maleate from mucoadhesive buccal patches.

This article describes buccal permeation of chlorpheniramine maleate (CPM) and its transbuccal delivery using mucoadhesive buccal patches. Permeation of CPM was calculated in vitro using porcine buccal membrane and in vivo in healthy humans. Buccal formulations were developed with hydroxyethylcellulose (HEC) and evaluated for in vitro release, moisture absorption, mechanical properties, and bioadhesion, and optimized formulation was subjected for bioavailability studies in healthy human volunteers.

Development and in vitro evaluation of buccoadhesive carvedilol tablets.

Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.

Development of nitrendipine transdermal patches: in vitro and ex vivo characterization.

Objective: The aim of the investigation was to develop and evaluate matrix type transdermal drug delivery systems (TDDS) of nitrendipine (NTDP).

Experimental: The matrix type TDDS of NTDP were prepared by solvent evaporation technique. Ten formulations (composed of Eudragit RL 100 and Hydroxypropyl methyl cellulose in the ratios of 5:0, 4:1, 3:2, 2:3, 1:4 in formulations A1, A2, A3, A4, A5 and Eudragit RS 100 and Hydroxypropyl methyl cellulose in the same ratios in formulation B1, B2, B3, B4, B5 respectively) were prepared.