Formulation and Taste Masking of Metronidazole Oral Disintegrating Tablets by a Novel Approach

The anti-protozoal drug, metronidazole, is developed as an oral disintegrating tablet (ODT) to treat amoebiasis and to bypass hepatic metabolism. The work aimed to prepare, taste-masking oral disintegrating tablets of metronidazole using different proportions of the drug and disintegrants in various ratios by an effervescent method. The ODT was developed by direct compression with various concentrations of super disintegrating agents (1-7%). In this technique, sodium bicarbonate and tartaric acid were used to generate effervescence. The formulated tablets were assessed for physicochemical characteristics. The results of FTIR spectroscopy indicated the stable character of metronidazole. In vitro studies revealed that batch F6 was having a 97.65% cumulative amount of drug release at 20th minute compared to other formulations. Due to the effervescent method, there was a significant increase in drug release, seen at the 1:1.5 ratio. Taste evaluation studies were conducted on healthy human volunteers.

A Validated specific Stability-Indicating Reversed-Phase High-Performance Liquid Chromatography Assay Method for L-Ornithine L-Aspartate and Silymarin, and their related Substances and its Application to Dissolution Studies

The present study was aimed at the development and successive validation of a novel, simple, sensitive, and stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) method for quantitative calculation of L-ornithine L-aspartate (LOLA) and Silymarin (SL), and also their relevant substances in bulk and pharmaceutical dosage forms. The chromatographic technic was optimized using the impurity-spiked solution. The separation of all the two active components and their impurities was achieved by a chromatographic method with an Agilent Eclipse XDB-C18, 150 × 4.6 mm, 3.5 μ column, using gradient elution with mobile phase A consisting of a mixture of 0.1% orthophosphoric acid and water and acetonitrile as mobile phase B. The instrumental settings included a flow rate of 1 mL/min for both related substances and assay, a detector wavelength of 225 nm, by using a PDA detector. The established method was validated according to the current ICH requirements. The detection limit and the limit of quantification for the two active components and their related impurities were established with respect to test concentration. The calibration graphs plotted were linear with a regression coefficient R2 andgt; 0.999, indicates the linearity of the method was within the limits. Recovery studies were satisfactory and the parameters, such as, specificity, linearity, accuracy, precision, and robustness were determined as part of the method validation. Moreover, using the same method dissolution study was performed on active pharma ingredients to estimate the recovery. The obtained results were within the range of acceptance criteria. These results suggest that the developed method was found to be applicable for routine analysis for testing chromatographic purity of LOLA and SL and it can be utilized for the calculation of both active ingredients and their impurities in tablet dosage forms.

Synthesis of Glibenclamide-Oxalic Acid Cocrystal using ThermalSolvent-Free Method

Solubility is an important parameter affecting the bioavailability of drugs. The solubility of an active pharmaceutical ingredient (API) could be improved through the formation of cocrystal, which is a crystalline complex composed of two or more different molecules. Glibenclamide (GCM) is an API with poor solubility in water, which belongs to class II, characterized as highly permeable with low solubility. Therefore, this study aimed to synthesize and characterize the cocrystal of GCM-oxalic acid (OA) using the melting method. The interaction between GCM-OA complexes was predicted using the in silico method. Also, the cocrystal complexes were characterized by differential scanning calorimetry (DSC), infrared (IR) spectrophotometry, and powder X-ray diffraction (PXRD), as well as, through solubility and dissolution tests. The result showed that GCM and OA have the potential of forming cocrystal through the in silico method. Also, the cocrystal of GCM-OA with a molar ratio 1:2, significantly improved the solubility and dissolution profile of GCM. In addition, the spectrum IR of cocrystal exhibited a shifting peak at 1,700 cm-1 indicating the presence of intermolecular interaction between GCM and OA. Furthermore, the DSC and PXRD analyses showed a new single endothermic peak and new diffraction peak pattern, respectively, indicating the formation of a new crystalline component.

Niosomes: Potential Nanocarriers for Drug Delivery

Niosomes are novel vesicular drug delivery systems, where the solution is surrounded by non-ionic surfactant vesicles. The niosomes offer different benefits over the traditional drug delivery system. Niosomes are structurally similar to liposomes, as they also consist of a bilayer. In the case of niosomes, the bilayer consists of non-ionic surface-active agents instead of phospholipids, as seen in liposomes. Niosomes are much more stable during the process of formulation and storage, as compared to liposomes. Niosomes may resolve the issues of insolubility, volatility, poor bioavailability, and rapid drug degradation. It has been discovered in recent years that, these vesicles can enhance drug bioavailability and can act as a new strategy to deliver many conventional therapeutic agents, such as, protein drugs, and gene materials. It is also easy to prepare and scale up this novel delivery system with low production costs. The delivery of drugs via niosomal formulations may be relevant to several pharmacological agents for their activity against different diseases. The present review provides an overview about the advantages and disadvantages, fabrication techniques, types, characterization technique, and different applications of niosomes.

Modification of Choline Derivatives and the Study of their Pharmacological Activity

Organicmoleculeshavebiologicalactivityforavarietyofstructuralfeatures,someactivitiesareassociatedwiththestructural basis of a known molecule, and others are associated with the type and orientation of additive modifications. However, acetylcholine (ACh) is the main neurotransmitter of the parasympathetic nervous system, the part of the autonomic nervous system that contracts smooth muscles, dilates blood vessels, increases body secretion, and slows the heartrate. Inthecentralnervoussystem,AChhasseveralrulesanditplaysanimportantroleinmemoryandlearning,aswellas,inthe abnormal deficiency of ACh in the brain in people with Alzheimer’s disease. In the past, it has been attempted to use ACh chlorideascholinergicstimulants,but,unfortunately,ithasbeenfoundthatitdoesnothavealastingeffectbecauseofitstoo short action duration due to its rapid hydrolysis by acetylcholinesterase (AChE) enzymes and the lack ofspecificity.

Comparative Hypoglycaemic Activity of Fixed Dose Combination Anti-Diabetic Formulations Versus Respective Monotherapies in Diabetic Rabbits

Type 2 diabetes mellitus is a disease of impaired glucose homeostasis and chronic hyperglycemia. Current approaches for the treatment frequently involving the use of combination therapy. The aim of the present study was to evaluate and compare the hypoglycaemic activity of fixed-dose combination anti-diabetic formulations and respective individual agents using rabbits as an animal model. Experimental diabetes was induced by a single intravenous injection of alloxan monohydrate at a dose of 150 mg/kg. Individual drugs and combination tablets were administered to experimental groups. Fasting blood glucose level was estimated at 0, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours using glucometer. Data were statistically analyzed using student t-test and p less than 0.05 considered as statistically significant. The reduction in fasting blood glucose level in diabetes-induced rabbits was significantly higher with combination products compared to individual drugs. Fixed-dose combination products had shown improved glycaemic control than individual agents. Fixed-dose combination therapy can be used as a suitable option for selected patients requiring multiple glucose-lowering therapies for use as an adjunct to diet and exercise to improve glycaemic control in type 2 diabetes mellitus.

Implementation of Quality by Design Approach to the Analytical Method Development and Validation for the Estimation of Rosuvastatin Calcium

Quality by Design (QbD) refers to the achievement of certain predictable quality with a predetermined and desired specification. The current studies details QbD enable the development of a simple, rapid, sensitive, and cost-effective high-performance liquid chromatographic method for the estimation of rosuvastatin calcium. The factor screening studies were performed using a 3-factor 12-trials 2-level factorial design. System thematic optimization was performed employing split-plot design by selecting the mobile phase ratio, buffer pH, and column type as the critical method parameter (CMPs) identified from screening studies, thus, evaluating a critical quality attribute (CQA), viz., retention time, peak tailing, and theoretical plate as per the parameter of the method robustness. The optimal chromatographic separation was achieved using acetonitrile and water 75:25 v/v as the mobile phase with a flow rate of 1 mL/min by using a PDA detector at 246 nm. The method was validated as per the ICH recommended conditions, which ensure a high degree of linearity, accuracy, precision, sensitivity, and robustness over the exiting liquid chromatography methods of the drug. Moreover, the lower solvent consumption along with the short analytical run time of 10 minutes leads to a cost-effective and environment-friendly chromatographic procedure. Thus, the proposed method reviled that rapid and represented a good procedure for rosuvastatin calcium.

Development and Validation of simple UV Spectrophotometric Method for the Determination of Racecodotril both in Bulk and Marketed Dosage Formulations

Racecodotril (RCT), (N-[2-[(acetylthio) methyl]-1- oxo- 3- phenyl propyl] -glycine phenylmethyl ester) is an enkephalinase inhibitor. A rapid, specific, and economic UV spectrophotometric two methods have been developed using a solvent composed of methanol to determine the RCT content in bulk and pharmaceutical dosage formulations. Method A is the absorbance maxima method, in which λmax is 231 nm, linearity was observed in the concentration range 10 to 100 μg/mL for all the two methods, and exhibited good correlation coefficient for method A (r2 = 0.9991) and excellent mean recovery (98.22–102.77%). Method B is the area under curve (AUC), in which λmax 226 to 236 nm was selected for estimation of RCT and exhibited a good correlation coefficient for method B (r2 = 0.9953). The method was validated statistically and by recovery studies for linearity, precision, repeatability, and reproducibility. The obtained results reveal that the method can be employed for the routine analysis of RCT in bulks, as well as, in the commercial formulations.

Development and Validation of RP-HPLC Method using Photodiode Array or Diode-Array Detection Detector for simultaneous Estimation of the Amlodipine Besylate and Lisinopril in Fixed-Dose Formulation

A basic and specific HPLC-PDA (high-performance liquid chromatography-photodiode array) detector showing approach was created for the simultaneous estimation of anti-hypertensive medications—amlodipine besylate (AMD) and lisinopril (LIS). A successful chromatography method was developed using the SunFire C8 column (4.6 × 150 mm, 5 μm) with gradient elution of the mobile phase composed of 85:25 potassium dihydrogen phosphate in water and methanol at a flow rate of 0.7 mL/min. The wavelength was set at 212 nm for the simultaneous estimation of AMD and LIS. The retention time obtained was 5.1 and 10.5 minutes for AMD and LIS, respectively. Descriptive performance of the proposed HPLC methodology was measurably approved as for framework accuracy, linearity, robustness, specificity, precision, and forced degradation for identification and evaluation limits. The linearity range for AMD and LIS correlation coefficient value obtained was R2 andgt; 0.999. The drugs were exposed to forced degradation conditions—acidic, alkali, oxidation, etc. The newly developed reverse phase high performance liquid chromatography (RP-HPLC) method was applied for the detection of the referred to anti-hypertensive medications in their combination pharmaceutical tablets.

Challenges of HPLC Method Development and Validation for the Assay of Bemotrizinol from Complex Matrix in Cosmeceutical Preparation

A simple high performance liquid chromatography (HPLC) method was developed for the assay of bemotrizinol (Tinosorb-S) from the complex pharmaceutical cosmetics matrix. Unlike the existing methods, the proposed mobile phase used in this method is very simple and excluding buffer. The use of buffer reducing column longevity and also a time-consuming process which increases the cost of analysis. To overcome all the referred problems, the present article was developed and validated as per International Council for Harmonization (ICH) guidelines. The reverse-phase chromatography was performed on Shimadzu model no. SPD-M10A VP with LC solution software, μBondapack (3.9 × 300 mm, 10-micron particle size) column with methanol (100%) as mobile phase at a flow rate 2.5 mL per minutes and UV detection at 254 nm. The retention time of bemotrizinol was found in 17.599 minutes, and the linear regression analysis data for the calibration plots showed a good linear relationship in the concentration range 70 to 130 μg/mL. The value of the correlation coefficient, slope, and intercept were 0.996, 7,715, and 15,320, respectively. The limit of quantification (LoQ) and limit of detection (LoD) were found to be 1.32 and 0.44, respectively. The relative standard deviation (RSD) for intra-day sample A 1.0858, sample B 0.8859, and inter-day sample A 0.9921, sample B 0.967 which were found to be lesser than 2%. The developed method was validated with regard to linearity, accuracy, precision, selectivity, and robustness, and the method was found to be simple, cost-effective, precise, accurate, linear, and specific for the successful identification and determination of bemotrizinol in pharmaceutical cosmetic preparation.