Sensitive high-performance liquid chromatographic determination of cyclizine and its demethylated metabolite, norcyclizine, in biological fluids using coulometric detection

An accurate, sensitive, selective and reproducible high-performance liquid chromatographic method with coulometric detection for the determination of cyclizine and its inactive demethylated metabolite, norcyclizine, in biological fluids has been developed. The drugs were separated using a custom packed reversed-phase C18 analytical column and phosphate buffer (0.05 M, pH 3)-acetonitrile (7:3) as mobile phase. The dual electrode coulometric detector was operated in the "oxidative-screen" mode with the upstream electrode (detector 1) set at 0.55 V and the downstream electrode (detector 2) set at 0.90 V. Serum and urine samples were prepared for analysis by solid-phase extraction, followed by a simple phase-separation step. The limit of quantitation was 1 ng/ml for both cyclizine and norcyclizine in serum and urine

Analytical methods for the quantitative determination of oxytocin

Oxytocin is a clinically important nonapeptide that is used for the induction and/or augmentation of labor and is normally administered as a slow intravenous infusion diluted with normal saline or Ringer’s lactate solution. Oxytocin is also indicated for use in the prevention and treatment of post partum hemorrhage and may be administered via either the intramuscular or intravenous routes in order to increase uterine tone and/or reduce bleeding. The analysis of oxytocin in different media has evolved over the past 30 years with the result that more sophisticated, selective and sensitive techniques are used for the determination of the compound. A variety of techniques have been applied to the determination of oxytocin in different matrices ranging from simple paper chromatography to hyphenated liquid chromatographic such as liquid chromatography coupled with mass-spectrometry. Additionally enzyme linked immuno-sorbent assays (ELISA) and radio immuno-assays (RIA) are used for the determination of low concentrations of oxytocin in biological matrices. This manuscript provides a systematic survey of the analytical methods that have been reported for isolation and quantitation of oxytocin in different matrices

Development and validation of a stability-indicating analytical method for the quantitation of oxytocin in pharmaceutical dosage forms

A single stability-indicating assay for oxytocin (OT) in pharmaceutical dosage forms using gradient elution over 21 min has been reported in the literature. Furthermore, published and compendial methods for the analysis of OT containing dosage forms also involve using HPLC with gradient elution and complicated mobile phases that include hydrophobic ion pairing agents. A simple isocratic and stability-indicating assay was developed and validated. The conditions are as follows, column: Phenomenex® C18 Hypersil, 5 μm packing, 4.6 mm × 150 mm with acetonitrile–phosphate buffer (pH 5; 0.08 M) (20:80) as the mobile phase with UV detection at 220 nm The method was found to be specific for OT in the presence of degradation products and chlorbutol (preservative) with an overall analytical run time of 16 min. Accuracy was determined to be 0.77–1.18% bias for all samples tested. Intra-assay precision (repeatability) was found to be 0.22–1.04%R.S.D. while the inter-day precision (intermediate precision) was found to be 1.27–1.68%R.S.D. for the samples studied. The calibration curve was found to be linear with the equation y = 1.81x + 0.02 and a linear regression coefficient of 0.9991 over the range 0.4–12.0 IU/ml. The LOD and the LOQ were determined to be 0.1 and 0.4 IU/ml, respectively. Syntocinon®, a commercially available dosage form of OT was assayed resulting in 100.5–106.6% recovery of the label claim and an average of 10.04 IU/ml

The comparison of in vitro release methods for the evaluation of oxytocin release from Pluronic® F127 parenteral formulations

The objective of these studies was to develop a discriminatory in vitro release test for assessing formulation factors that may affect oxytocin (OT) release during formulation development studies of a Pluronic® F127 OT in situ gel-forming parenteral dosage form. An appropriate release assessment method should be able to discriminate between the performance of different formulation compositions (1, 2), and this was the primary criterion used for selection of an appropriate test procedure during the test method development process. ANOVA and the difference (f1) and similarity (f2)factors were used to evaluate the discriminatory behavior of different test methods that were investigated in these studies. The in vitro release tests that were investigated included the use of USP Apparatus 1, 2, and 3; a dialysis bag in USP Apparatus 2; and a membrane-less diffusion method. It was concluded that the use of USP Apparatus 3 was best able to discriminate between OT release for the different formulations tested. USP Apparatus 3 was thus considered the most suitable in vitro release test apparatus for studying formulation factors affecting OT release during the development of a parenteral dosage form prepared using Pluronic® F127

The effects of buffer molarity, agitation rate and mesh size on verapamil release from modified release mini-tablets using USP Apparatus 3

The effects of agitation rate, buffer molarity,and mesh size on the dissolution rate of verapamil hydrochloride from sustained release matrix tablets were studied using USP Apparatus 3. Eudragit® and Carbopol® were used as rate-retarding polymers in tablets prepared by wet granulation.The study was conducted to determine whether the drugs exhibit similar release characteristics when tested under the same dissolution conditions. It was found that the dissolution rate of verapamil hydrochloride was affected by the variables assessed in these studies

Evaluation of the kinetics and mechanism of drug release from Econazole nitrate nanosponge loaded Carbapol Hydrogel

The objective of this study was to investigate the mechanism of release of econazole nitrate (EN) nanosponges loaded hydrogel and to compare it with EN hydrogel so as to develop an extended release topical drug delivery system of EN. Nanosponges of EN were prepared using ethyl cellulose and PVA by emulsion solvent evaporation method. On the basis of pharmacotechnical evaluation nanosponges with least particle size of 230.1 nm and good rheological properties were formulated as hydrogel (F1 – F7). In vitro drug release data of EN nanosponges loaded hydrogels in phosphate buffer pH 6.8 and 7.4 when analysed by GraphPad Prism software version 4.0 San Diego, USA best fitted the Makoid-2 Banakar model (R value greater than 0.98). The Korsmeyer-Peppas release exponent (n) ranged between 0.331 – 0.418, which confirmed diffusion as the principle mechanism of drug release. The release mechanism was further confirmed by calculating the ratio of exponents A/B ratio derived from the Kopcha model

Role of percutaneous penetration enhancers

It is clear that scientists are now only beginning to comprehend the complexity of transdermal drug delivery. Elucidation of the biochemical composition and functioning of the intrinsic diffusional barrier of the stratum corneum has prompted investigation of chemical and physical means of enhancing the percutaneous penetration of poorly absorbed drugs. Chemical enhancers that aid absorption of co-administered moieties are currently believed to improve solubility within the stratum corneum or increase lipid fluidity of the intracellular bilayers. Alternatively,the use of ionto- or phonophoresis may facilitate the absorption of some drug molecules by physical alteration of the barrier. The role of penetration enhancer inclusion in topical formulations has been well documented and will undoubtedly, in the future, permit the delivery of broader classes of drugs through the stratum corneum

Analysis of macrolide antibiotics

The following macrolide antibiotics have been covered in this review: erythromycin and its related substances, azithromycin, clarithromycin, dirithromycin, roxithromycin, flurithromycin, josamycin, rokitamycin, kitasamycin, mycinamycin, mirosamycin, oleandomycin, rosaramicin, spiramycin and tylosin. The application of various thin-layer chromatography, paper chromatography, gas chromatography, high-performance liquid chromatography and capillary zone electrophoresis procedures for their analysis are described. These techniques have been applied to the separation and quantitative analysis of the macrolides in fermentation media, purity assessment of raw materials, assay of pharmaceutical dosage forms and the measurement of clinically useful macrolide antibiotics in biological samples such as blood, plasma, serum, urine and tissues. Data relating to the chromatographic behaviour of some macrolide antibiotics as well as the various detection methods used, such as bioautography, UV spectrophotometry, fluorometry, electrochemical detection, chemiluminescence and mass spectrometry techniques are also included

Optimization of salbutamol sulfate dissolution from sustained release matrix formulations using an artificial neural network

An artificial neural network was used to optimize the release of salbutamol sulfate from hydrophilic matrix formulations. Model formulations to be used for training, testing and validating the neural network were manufactured with the aid of a central composite design with varying the levels of Methocel® K100M, xanthan gum, Carbopol® 974P and Surelease® as the input factors. In vitro dissolution time profiles at six different sampling times were used as target data in training the neural network for formulation optimization. A multi layer perceptron with one hidden layer was constructed using Matlab®, and the number of nodes in the hidden layer was optimized by trial and error to develop a model with the best predictive ability. The results revealed that a neural network with nine nodes was optimal for developing and optimizing formulations. Simulations undertaken with the training data revealed that the constructed model was useable. The optimized neural network was used for optimization of formulation with desirable release characteristics and the results indicated that there was agreement between the predicted formulation and the manufactured formulation. This work illustrates the possible utility of artificial neural networks for the optimization of pharmaceutical formulations with desirable performance characteristics

The use of response surface methodology to evaluate the impact of level 2 SUPAC–IR changes on the in vitro release of metronidazole and ranitidine from a fixed-dose combination tablet

The purpose of this study was to evaluate the effect of different levels of disintegrant (croscarmellose sodium, CCS), binder (polyvinylprrolidone K30, PVP–K30), and lubricant (magnesium stearate) on the in vitro release of metronidazole (MTZ) and rantidine (RTD) from a solid oral fixed-dose combination tablet. The excipient levels investigated were Level 2 changes in component and composition described in the Scale-Up and Post Approval Changes for Immediate Release (SUPAC–IR) guidance (1). Batches of tablets (1000 units) were manufactured by wet granulation using a Saral high-shear mixer granulator and a Manesty B3B rotary tablet press. Weight uniformity, friability, and disintegration of all tablets were assessed, and all batches complied with compendial specifications. The amount of drug released (Q) at ten minutes was dependent on the levels of CCS in the formulation, and the effect of PVP–K30 and magnesium stearate was dependent on the levels of CCS. Synergistic interactions between independent variables were observed for the Q10 value for RTD, whereas PVP–K30 and magnesium stearate exhibited an antagonistic effect on the Q10 values for MTZ and RTD. The use of response surface methodology facilitated an investigation into the effect of Level 2 component and composition changes, as described in SUPAC–IR, on the in vitro release of MTZ and RTD from a fixed-dose combination (FDC) solid oral dosage form (SODF)