DETERMINATION OF ATORVASTATINE IN PHARMACEUTICAL FORMULATIONS BY REVERSE PHASE-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

A simple, sensitive and reproducible reverse-phase high performance liquid chromatographic (RP-HPLC) method has been developed for the quantitative estimation of Atorvastatin calcium (ATOR-C) in the pharmaceutical formulations. Chromatographic separation was achieved on a 250 4.6 mm, 5?, Waters symmetry column. The flow rate was 1mL/min and eluent was monitored by absorbance at 246.0 nm using a mixture of Methanol and Acetonitrile (pH 3.00.01) in the ratio of 25:75 (v/v). The retention times of ATOR-C was found to be 5.5 min. Calibration plots were linear in the concentration range of 5-25 ?g/mL for ATOR-C calcium. The total run time was 12 min. The proposed method was validated by testing its linearity, recovery, specificity, system suitability, precision (Interday, intraday, analyst and instrument precision), robustness and LOD/LOQ values and it was successfully employed for the determination of ATOR-C in pharmaceutical tablet formulations

Recent approaches for impurity profiling of pharmaceuticals

Impurities must be monitored carefully to assure the quality of drugs. It is important to identify potential sources of such impurities. Selective analytical methods need to be developed to monitor them. Methodology aspects for impurity investigations are discussed along with an emphasis on understanding the origin and fate of impurities to guide decisions on process controls and specifications. Orthogonal analytical approaches for impurity investigations to provide a complete understanding of a drug substance impurity profile. Considerations for control of toxic impurities include sensitive and selective analytical methodology and determination of the process capability for removing the impurity. New impurities may be observed as changes are made in the synthesis, formulation, or production procedures, albeit for improving them. At times it is necessary to isolate and characterize an impurity when hyphenated methods do not yield the structure or when confirmation is necessary with an authentic material

Review: Development of forced degradation studies of drugs

Forced degradation studies show the chemical behavior of the molecule which in turn helps in the development of formulation and package. A forced degradation study is an essential step in the design of a regulatory compliant stability program for both drug substances and products, and formalized as a regulatory requirement in ICH Guideline Q1A in 1993. Forced degradation is a degradation of new drug substance and drug product at conditions more severe than accelerated conditions. It is required to demonstrate specificity of stability indicating methods and also provides an insight into degradation pathways and degradation products of the drug substance and helps in elucidation of the structure of the degradation products. Thus, this review discusses the current trends in performance of forced degradation studies by providing a strategy for conducting studies on degradation mechanisms

Phyllanthus Niruri: A magic Herb

Medicinal herbs are significant source of pharmaceutical drugs. Latest trends have shown increasing demand of phytodrugs and some medicinal herbs have proven hepatotprotective potential. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partially propagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP’s). DAMPs perpetuate inflammation through the release of proinflammatory cytokines, but may also inhibit anti-inflammatory cytokines

Development of validated stability indicating assay method for simultaneous estimation of Diclofenac Sodium and Misoprostol in their combined dosage form

A Stability indicating Reverse-Phase liquid chromatographic method for the simultaneous estimation of DF and MP was developed. The chromatographic assay involves the use of Hi Q C18 W, 150 x 4.6mm, 5m column with a simple mobile phase composition of Acetonitrile and HPLC Grade water in the ratio of 70:30%v/v at a flow rate of 1mL/min with U.V detection at wavelength of 220 nm. The method showed good linearity in the concentration range of 50-100 ?g/mL for DF and 0.20-0.40 ?g/mL for MP. The proposed method was also successfully applied to 20 tablets of marketed formulation (Arthotec). The developed method was successfully validated as per the ICH guidelines for following parameters. Accuracy, precision, repeatability, ruggedness, robustness, system suitability tests, etc. The RSD for Intra-day and Inter-day precision was found to be 0.96-1.85, 1.02-1.83 For DF and 0.55-0.59, 0.59-0.63 for MP. The average percentage recoveries for DF were found to be 90.83, 99.74, 100.21 and for MP it was found to be 100.83, 98.94, 99.72. which was in good agreement with labeled amount of Pharmaceutical formulation. The stability indicating capacity was tested by accelerated degradation of marketed formulation in acidic (0.1 N HCl), basic (0.1 N NaOH), Neutral (water), Oxidative (3% H 2 O 2 ), Thermal (60 0 C), Sunlight exposure

STUDIES ON BIOAVAILABILITY ENHANCEMENT OF CURCUMIN

Objective: The objective of the present work was to improve aqueous solubility and in vivo bioavailability of curcumin and structural analogues of curcumin such as potassium, calcium, magnesium salts and nitro derivative. Methods: Structural analogues of curcumin were prepared by reaction of curcumin with potassium chloride, magnesium chloride hexahydrate and calcium chloride dihydrate in a suitable solvent. The nitro derivative synthesized by treating curcumin with sulphuric acid and nitric acid. The prepared analogues were evaluated for melting behavior, solubility, UV spectrophotometry, partition coefficient, moisture content, cellular uptake, FTIR analysis, antimicrobial activity and in vivo bioavailability in the rat. Results: Chemical modification of curcumin increased the saturation solubility to 11.6, 16.5, 21.5, 28.0 µg/ml in calcium salt, magnesium salt, potassium salt and nitro derivative respectively, against 8.6 µg/ml of curcumin. The analogues were chemically stable as curcumin analyzed by FTIR spectrophotometry. Increased cellular uptake, as well as enhanced antimicrobial activity, was demonstrated by modified curcumin analogues. Moreover, significant improvement in plasma levels was estimated with nitro derivative. Conclusion: The present work recommends that nitration of curcumin improves aqueous solubility which may improve absorption and in vivo bioavailability

STABILITY INDICATING RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF RABEPRAZOLE SODIUM AND LEVOSULPIRIDE IN CAPSULE DOSAGE FORM

A Stability indicating Reverse-Phase liquid chromatographic method for the simultaneous estimation of RPS and LSP was developed. The chromatographic assay involves the use of C 18 Column (150 4.6mm, with particle size 5?m) with a simple mobile phase composition (Phosphate Buffer pH-3.3 and Methanol 55:45 v/v) at a flow rate of 1mL/min with U.V detection at wavelength of 230 nm. The method showed good linearity in the concentration range of 90.0-210.0 ?g/mL for LSP and 24.056.0 ?g/mL for RPS. The proposed method was also successfully applied to 20 tablets of marketed formulation (Neopride). The developed method was successfully validated as per the ICH guidelines for following parameters. Accuracy, precision, repeatability, ruggedness, robustness, system suitability tests, etc. The RSD for Intra-day and Inter-day precision was found to be 1.02-1.83, 0.96-1.42 For LSP and 0.55-0.59, 0.75-0.63 for RPS. Average Percent recovery was found to be 980.2, 100.570.2, 99.800.2 for LSP and 101.380.2, 98.670.2, 99.530.2 for RPS which was a good agreement with labeled amount of pharmaceutical formulation. The stability indicating capacity was tested by accelerated degradation of marketed formulation in acidic (0.1 N HCl), basic (0.1 N NaOH), Neutral (water), Oxidative (3% H 2 O 2 ), Thermal (60 0 C), Sunlight exposure

Controlled release effervescent buccal discs of buspirone hydrochloride: <i>in vitro</i> and <i>in vivo</i> evaluation studies

<p>In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and <i>in vitro</i> drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. <i>In vivo</i> animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs <i>in vitro</i> and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form.</p

Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 32 Factorial Design to Improve Solubility and In Vitro Bioavailability

Piroxicam is a Biopharmaceutical Classification System (BCS) Class II drug having poor aqueous solubility and a short half-life. The rationale behind the present research was to develop a Piroxicam nanosuspension to enhance the solubility and thereby the in vitro bioavailability of the drug. Piroxicam nanosuspension (PRX NS) was prepared by an anti-solvent precipitation technique and optimized using a full-factorial design. Herein, the nanosuspension was prepared using polymer polyvinylpyrrolidone (PVP) K30&reg; and Poloxamer 188&reg; as a stabilizer to improve the solubility and in vitro bioavailability of the drug. Nine formulations were prepared based on 32 full-factorial experimental designs to study the effect of the formulation variables such as concentration of poloxamer 188 (%) (X1) and stirring speed (rpm) (X2) as a process variable on the response of particle size (nm) and solubility (&micro;g/mL). The prepared NS was characterized by phase solubility, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), transmission electron microscopy (TEM), particle size, zeta potential, entrapment efficiency, and percent drug release. DSC and XRPD analysis of freeze-dried NS formulation showed conversion of PRX into a less crystalline form. NS formulations showed a reduction in the size from 443 nm to 228 nm with &minus;22.5 to &minus;30.5 mV zeta potential and % drug entrapment of 89.76 &plusmn; 0.76. TEM analysis confirmed the size reduction at the nano level. The solubility was increased from 44 &mu;g/mL to 87 &mu;g/mL by altering the independent variables. The solubility of PRX NS in water was augmented by 14- to 15-fold (87.28 &mu;g/mL) than pure PRX (6.6 &mu;g/mL). The optimized formulation (NS9) at drug-to-stabilizer concentration exhibited a greater drug release of approximately 96.07% after 120 min as compared to the other NS formulations and pure PRX (36.78%). Thus, all these results revealed that the prepared NS formulations have improved the solubility and in vitro dissolution compared to the pure drug. Furthermore, an increase in the drug release was observed from the NS than that of the pure PRX. All these outcomes signified that the prepared PRX NS showed an increase in solubility and in vitro dissolution behavior; which subsequently would aid in attainment of enhanced bioavailability