Terpenoids as potential phytoconstituent in the treatment of diabetes: From preclinical to clinical advancement.

Background: Diabetes mellitus, a hyperglycemic condition associated with multitudinous organ dysfunction, is a hallmark of the metabolic disorder. This life-threatening condition affects millions of individuals globally, harming them financially, physically and psychologically in the course of therapy.

Purposes: The course therapy for illnesses has undergone ground-breaking transformations due to recent technical advances and insights.

Development of direct compression Acetazolamide tablet with improved bioavailability in healthy human volunteers enabled by cocrystallization with p-Aminobenzoic acid.

Pharmaceutical cocrystallization has been widely used to improve physicochemical properties of APIs. However, developing cocrystal formulation with proven clinical success remains scarce. Successful translation of a cocrystal to suitable dosage forms requires simultaneously improvement of several deficient physicochemical properties over the parent API, without deteriorating other properties critical for successful product development.

Advanced Dome cellulose/alginate/chitosan composite matrix design with gastric and intestinal co-targeting capacities.

Dome matrix was designed with gastric and intestinal targeting capacities using melatonin and caffeine as model drugs, and alginate, chitosan and cellulose as composite materials. The melatonin, caffeine and intermediate hydroxypropylmethylcelluose-based dispersible modules were prepared through compaction. Caffeine piled module was capped at both ends with melatonin void modules via intermediate dispersible modules into Dome matrix.

pH-Responsive Copolymeric Network Gel Using Methacrylated β-Cyclodextrin for Controlled Codelivery of Hydrophilic and Hydrophobic Drugs.

In medical science, sometimes two drugs with different solubilities are simultaneously required in combination to treat various diseases. Herein, a pH-responsive, copolymeric, antioxidant, biocompatible, and chemically crosslinked network gel is prepared to explore its capability as a matrix for controlled release of both hydrophobic [ibuprofen (IB)] and hydrophilic [tetracycline hydrochloride (TCH)] drugs, simultaneously. This three-dimensional β-CD-Meth-cl-(PHPMA--PAAc) network hydrogel is synthesized via two steps: (I) methacrylation of β-cyclodextrin and (II) grafting of poly(hydroxypropyl methacrylate) and poly(acrylic acid), followed by crosslinking of poly(ethylene glycol) diacrylate onto the backbone of methacrylated β-cyclodextrin (β-CD-Meth).

Investigating the Role of the Reduced Solubility of the Pirfenidone-Fumaric Acid Cocrystal in Sustaining the Release Rate from Its Tablet Dosage Form by Conducting Comparative Bioavailability Study in Healthy Human Volunteers.

Pirfenidone (PFD) is the first pharmacological agent approved by the US Food and Drug Administration (FDA) in 2014 for the treatment of idiopathic pulmonary fibrosis (IPF). The recommended daily dosage of PFD in patients with IPF is very high (2403 mg/day) and must be mitigated through additives. In the present work, sustained-release (SR) formulations of the PFD-FA cocrystal of two different strengths such as 200 and 600 mg were prepared and its comparative bioavailability in healthy human volunteers was studied against the reference formulation PIRFENEX (200 mg).

Design of multi-particulate "Dome matrix" with sustained-release melatonin and delayed-release caffeine for jet lag treatment.

Multi-particulate Dome matrix with sustained-release melatonin and delayed-release caffeine was designed to restore jet lag sleep-wake cycle. The polymeric pellets were produced using extrusion-spheronization technique and fluid-bed coated when applicable. The compact and Dome module were produced by compressing pellets with cushioning agent.

Coatless alginate pellets as sustained-release drug carrier for inflammatory bowel disease treatment.

Conventional alginate pellets underwent rapid drug dissolution and failed to exert colon targeting unless subjected to complex coating. This study designed coatless delayed-release oral colon-specific alginate pellets for ulcerative colitis treatment. Alginate pellets, formulated with water-insoluble ethylcellulose and various calcium salts, were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed reaction to initiate only in dissolution.

Drug release, preclinical and clinical pharmacokinetics relationships of alginate pellets prepared by melt technology.

Introduction: Alginate pellets prepared by the aqueous agglomeration technique experience fast drug dissolution due to the porous pre-formed calcium alginate microstructure.

Objective: This study investigated in vitro drug release, preclinical and clinical pharmacokinetics relationships of intestinal-specific calcium acetate-alginate pellets against calcium-free and calcium carbonate-alginate pellets.

Method: Alginate pellets were prepared by solvent-free melt pelletization instead of aqueous agglomeration technique using chlorpheniramine maleate as model drug.

Microwave assisted synthesis of acrylamide grafted locust bean gum and its application in drug delivery.

Acrylamide grafted copolymer of locust bean gum was prepared by microwave irradiation using ceric ammonium nitrate as redox initiator. The grafting process was optimized in terms of irradiation time, amount of initiator and acrylamide by using constant amount of native locust bean gum. The grafted gum was characterized by Fourier transform infrared spectroscopy (FT-IR), (13)C nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), X-ray diffraction study (XRD), differential scanning calorimetry (DSC), elemental analysis, contact angle, viscosity, molecular weight, swelling and biodegradability studies.

Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics.

The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design).

Convolution and validation of in vitro-in vivo correlation of water-insoluble sustained-release drug (domperidone) by first-order pharmacokinetic one-compartmental model fitting equation.

The experimental study presents a brief and comprehensive perspective on the methods of developing a Level A in vitro-in vivo correlation (IVIVC) for extended oral dosage forms of water-insoluble drug domperidone. The study also evaluates the validity and predictability of in vitro-in vivo correlation using the convolution technique by one-compartmental first-order kinetic equation. The IVIVC can be substituted as a surrogate for in vivo bioavailability study for the documentation of bioequivalence studies as mandatory from any regulatory authorities.

Modulation of drug (metoprolol succinate) release by inclusion of hydrophobic polymer in hydrophilic matrix.

The objective of this study was to develop sustained release (SR) matrix tablets of metoprolol succinate (MS), by using different polymer combinations and fillers, to optimize by response surface methodology and to evaluate biopharmaceutical parameters of the optimized product. Matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC); and lactose and dibasic calcium phosphate dihydrate (DCP) as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design).

Determination of gemifloxacin in different tissues of rat after oral dosing of gemifloxacin mesylate by LC-MS/MS and its application in drug tissue distribution study.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to evaluate the accumulation of gemifloxacin in different tissues of Wister albino rat. The analytical method consists of the homogenization of tissues followed by simple liquid-liquid extraction and determination of gemifloxacin by an LC-MS/MS. The analyte was separated on a Peerless basic C(18) column (33 mm x 4.

Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.

The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.

Convulsant activity and pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of gemifloxacin in rats.

A pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was used to investigate the epileptogenic activity of gemifloxacin as a representative antibiotic with concentration-dependent antimicrobial activity. Rats received an intravenous infusion of gemifloxacin at a rate of 4 mg kg of body weight(-1) min(-1) over 50 min. Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion.

Comparative bioavailability study of amisulpride tablets in healthy Indian volunteers.

An improved HPLC method was developed and validated for the determination of concentration of amisulpride (CAS 71675-85-9) in human plasma, an attempt to compare the bioavailability of two amisulpride tablet formulations (reference and test) containing 200 mg of amisulpride. Both the formulations were administered orally as a single dose, separated by washout period of 1 week. This HPLC method validated by examining the precision and accuracy for the inter-day and intra-day runs in a linear concentration range of 50-1200 ng/ml.

Evaluation of the bioequivalence of two faropenem formulations in healthy Indian subjects.

This paper presents the results of a two-period, two-treatment, crossover study conducted in 12 Indian male volunteers under fasting conditions to assess the bioequivalence of two oral formulations (Reference and Test) containing 200 mg of faropenem (CAS 106560-14-9). Both of the formulations were administered orally as a single dose separated by a washout period of 1 week. The content of faropenem in plasma was determined by a validated HPLC method with UV detection.

Determination of ranolazine in human plasma by LC-MS/MS and its application in bioequivalence study.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantification of ranolazine in human plasma. The analytical method consists in the precipitation of plasma sample with methanol, followed by the determination of ranolazine by an LC-MS/MS. The analyte was separated on a Peerless Cyano column (33 mm x 4.

Extended release dosage form of glipizide: development and validation of a level A in vitro-in vivo correlation.

Defining a quantitative and reliable relationship between in vitro drug release and in vivo absorption is highly desired for rational development, optimization, and evaluation of controlled-release dosage forms and manufacturing process. During the development of once daily extended-release (ER) tablet of glipizide, a predictive in vitro drug release method was designed and statistically evaluated using three formulations with varying release rates. In order to establish internally and externally validated level A in vitro-in vivo correlation (IVIVC), a total of three different ER formulations of glipizide were used to evaluate a linear IVIVC model based on the in vitro test method.

Simultaneous determination of metoprolol succinate and amlodipine besylate in human plasma by liquid chromatography-tandem mass spectrometry method and its application in bioequivalence study.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of metoprolol succinate (MPS) and amlodipine besylate (AM) using hydrochlorothiazide (HCTZ) as IS in human plasma. Both the drugs were extracted by simple liquid-liquid extraction with chloroform. The chromatographic separation was performed on a reversed-phase peerless basic C18 column with a mobile phase of methanol-water containing 0.

Optimization of metformin HCl 500 mg sustained release matrix tablets using Artificial Neural Network (ANN) based on Multilayer Perceptrons (MLP) model.

The aim of the present study was to apply the simultaneous optimization method incorporating Artificial Neural Network (ANN) using Multi-layer Perceptron (MLP) model to the development of a metformin HCl 500 mg sustained release matrix tablets with an optimized in vitro release profile. The amounts of HPMC K15M and PVP K30 at three levels (-1, 0, +1) for each were selected as casual factors. In vitro dissolution time profiles at four different sampling times (1 h, 2 h, 4 h and 8 h) were chosen as output variables.

Bioequivalence study of a sustained release fixed dose combination capsule containing esomeprazole and domperidone in healthy subjects.

Objective: The study was designed to determine the relative bioavailability of two sustained release fixed dose combination (FDC) products of two manufacturers containing esomeprazole (CAS 326602-80-6) 40 mg and domperidone (CAS 57808-66-9) 30 mg in 24 healthy male volunteers. The pharmacokinetics of esomeprazole and domperidone individually after oral administration of tablet formulation has been extensively evaluated in adult volunteers. However, no published data are available regarding the combined pharmacokinetics and bioavailability of this particular FDC.