M. H. G. Dehghan

HPTLC Method for the Simultaneous Estimation of Emtricitabine and Tenofovir in Tablet Dosage Form

A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed and validated for the estimation of emtricitabine and tenofovir simultaneously in combined dosage form. The stationary phase used was precoated silica gel 60F 254. The mobile phase used was a mixture of chloroform: methanol (9:1 v/v). The detection of spots was carried out at 265 nm. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found to be linear between 200 to 1000 ng with regression coefficient of 0.9995. The proposed method can be successfully used to determine the drug content of marketed tablet formulation.

Histone Deacetylases as Targets for Multiple Diseases

Inhibition of Histone deacetylases (HDACs) has been emerged as important approach to reverse aberrant epigenetic changes associated with various cancerous and non-cancerous diseases. The field of histone deacetylase inhibitors (HDIs) is moving into a new phase of development. The structure of histone deacetylases is well-established and the active sites have been well identified. Various drugs targeting this enzyme are in the pipeline for the treatment of different diseases. Since first-generation HDAC inhibitors proved their clinical fruitfulness and also second generation inhibitors are rationally designed with improved specificity, experts believe that this class will emerge in the treatment of various diseases. Considering these facts present review focuses on HDACs and developments of HDIs in the treatment of various diseases.

Assessment of Isomalt for Colon-Specific Delivery and Its Comparison with Lactulose

Lactulose is used as a triggering substance in a unique colon-specific delivery technology called CODESTM. Colonic microflora degrades lactulose and forms short-chain fatty acids to activate the CODESTM system. However, lactulose has been reported to cause a Maillard-type reaction with substances containing primary or secondary amino groups that may produce carcinogenic compounds. Thus, the aim of this study was to look into the possibility to substitute lactulose with isomalt for fabrication of CODESTM. The in vitro degradation of both sugars before incorporating them into the CODESTM system was evaluated with the help of rat caecal microflora. The results showed that isomalt was less efficient with regard to its rate and extent of degradation into short-chain fatty acids by the microflora compared to lactulose. However, the in vitro dissolution study did not show a significant difference in the performance between lactulose and isomalt when they were incorporated separately in CODESTM. A similar result was also obtained in the in vivo study. Based on the above results, isomalt could be used as an alternative to lactulose for colonic delivery system utilizing the principles of CODESTM.

Development and Validation of a Dissolution Method for Pioglitazone Tablets

Dissolution testing has emerged in the pharmaceutical field as a very important tool to characterize drug product performance. Pioglitazone hydrochloride, a frequently prescribed antidiabetic, has no dissolution assay in official monographs. The aim of the study was to develop and validate a dissolution test for the quality control of pioglitazone hydrochloride (PH) tablets containing 15 mg of active pharmaceutical ingredient (API). Results from testing sink conditions and stability at 37 ° C show that PH is stable in potassium chloride buffer at pH 1.2, 1.5, 1.8, and in 0.1 N hydrochloric acid. In vitro dissolution tests of PH tablets were performed using different test conditions but always under sink conditions. The effects of filtration and deaeration were evaluated. The most discriminatory test conditions, potassium chloride buffer at pH 1.5 (900 mL at 37 ± 0 .5 ° C) as dissolution medium, paddle method (Apparatus 2), 75 rpm, and 60 min, were satisfactory. The UV spectrophotometric method for determination of released PH was developed and validated. The method presented linearity (r 2 = 0.999) in the concentration range of 10–60 μg/mL. The recoveries were good, ranging from 96.407% to 100.24%. The intraday and interday precision results were 1.704% and 1.3869% RSD, respectively. The developed dissolution test is adequate for its purpose and can be applied for the quality control of 15-mg PH tablets.

Quality by design approach for development of suspension nasal spray products: a case study on budesonide nasal suspension

Abstract The objective of this study was to provide quality by design (QbD) approach for development of suspension type nasal spray products. Quality target product profile (QTPP) of test product budesonide nasal suspension (B-NS) was defined and critical quality attributes (CQAs) were identified. Critical formulation, process and delivery device variables were recognized. Risk assessment was performed by using failure mode and effect analysis (FMEA) methodology. Selected variables were further assessed using a Plackett Burman screening study. A response surface design consisting of the critical factors was used to study the interactions between the study variables. Formulation variable X2: median particle size of budesonide (D50) (µ) has strikingly influenced dissolution (%) (Y1), while D50 droplet size distribution (µm) (Y2) was significantly impacted by formulation variable X1: Avicel RC 591 (%) and process variable X4: homogenization speed (rpm). A design space plot within which the CQAs remained unchanged was established at lab scale. A comprehensive approach for development of B-NS product based on the QbD methodology has been demonstrated. The accuracy and robustness of the model were confirmed by comparability of the predicted value generated by model with the observed value.

Enhanced Bioavailability and Dissolution of Atorvastatin Calcium from Floating Microcapsules using Minimum Additives.

Atorvastatin calcium, a lipid-lowering drug, is much less bioavailable because of reduced solubility in acidic media. Multiple-unit floating microcapsules of Atorvastatin calcium (ATC) were developed to expand the gastric residence time of the drug, as ATC has maximum rate of absorption in the upper GI tract. Floating microcapsules were prepared by Emulsion-solvent evaporation technique through incorporation of dioctyl sodium sulphosuccinate (DSS) as a dissolution enhancer. The microcapsules were assessed for shape, size, drug entrapment efficiency, stability and in-vitro drug dissolution rate and were subjected to SEM, DSC and PXRD studies. The ATC-loaded floating microcapsules were spherical in shape and had the particle size of about 28.10 μm and drug-loading efficiency of about 96.55 %. The floating microspheres containing DSS had significantly higher drug dissolution rates than those without DSS. The best formulation, AT4, consisting of Ethyl cellulose, DSS and Poly Ox®, had a maximum drug dissolution rate of 97.86 %, as compared to Storvas 80 mg (Ranbaxy Ltd, as a reference) which had a rate of only 54% during a period of 12 h in acidic media. A pharmacokinetic study performed on albino rabbits illustrates that the bioavailability of AT4 floating microcapsules significantly increased to nearly 1.7 times that of Storvas 80 mg. The present study indicates that the use of multi-unit floating microcapsules for delivery of ATC can improve its bioavailability.

Quality by design (QbD) approach for design and development of drug-device combination products: a case study on flunisolide nasal spray

Abstract The objective of the present study was to design and develop drug-device combination product in particular flunisolide nasal spray (FNS) using quality by design (QbD) approach. Quality target product profile (QTPP) of FNS was defined and critical quality attributes (CQAs), i.e. viscosity (cp) (Y1) and D50 droplet size distribution (DSD) (μm) (Y2) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tools. Plackett–Burman and Box–Behnken designs were used for screening the significant factors and optimizing the variables range, respectively. It was observed that viscosity (cp) (Y1) was significantly impacted by formulation variables X1: propylene glycol (PG) (%) and X2: polyethylene glycol (PEG) 3350 (%), while D50 DSD (μm) (Y2) was significantly impacted by formulation variables X1: PG (%), X2: PEG 3350 (%) and device variable X8: delivery volume (μl). A design space plot within which the CQAs remained unchanged was established at laboratory scale. In conclusion, this study demonstrated how QbD based development approach can be applied to the development of drug-device combination products with enhanced understanding of the impact of formulation, process and device variables on CQAs of drug-device combination products.

Characterization and In Vitro Evaluation of Freeze-Dried Nasal Insert Composed of Chlorpheniramine Maleate with Ionic and Nonionic Polymer for Intranasal Delivery

In this study, the authors report the fabrication of nasal delivery system, termed nasal insert, and was carried out with ionic and nonionic polymer(s). The data revealed that nonionic polymer has less water uptake and low mucoadhesion time in comparison to the ionic polymers. With ionic polymers, relaxation of entangled polymer from the gel was toward lesser extent, thereby providing sustained release during in vitro release. The SEM images show more compact nature of ionic polymer when compared with nonionic polymer. Histopathology and in vitro permeation study conducted using sheep nasal mucosa showed significantly higher drug permeation from nonionic polymer.