The Development and the Validation of a Novel Dissolution Method of Favipiravir Film-Coated Tablets

The aim of this study was to develop and validate a dissolution test for favipiravir release in a tablet dosage form using ultra-high performance liquid chromatography (UHPLC). The dissolution method was developed by testing the solubility of favipiravir in media with different pH values. The results demonstrated that the best dissolution was achieved in phosphate buffer with a pH of 6.8. The amount of favipiravir that was released was about 100% after 30 min. The UHPLC method presented linearity (R = 1.000) in the concentration range of 0.044–0.44 mg/mL. The recovery parameter that was achieved ranged from 102.5% to 104.2%. The system suitability, repeatability, and intermediate precision RSD% results were found to be 0.36%, 1.99%, and 2.49%, respectively. In addition to these parameters and results, an F-test was performed using the Minitab 18 Statistical Software program for the intermediate precision and repeatability results. The standard and sample solutions were found to be stable for 2 days in their respective dissolution medium. This analytical method was also found to be selective for favipiravir. In conclusion, a simple and feasible dissolution method with a short run time of 2.5 min was developed and validated successfully. The obtained results demonstrated that the dissolution test developed here is adequate for its purpose and can be applied as the dissolution method for favipiravir in film-coated tablets for release analyses.

IMPROVEMENT OF THE DISSOLUTION PROFILE OF SIMVASTATIN TABLETS WITH THE ADDITION OF CREMOPHOR-EL USING WET GRANULATION METHOD

Objective: Simvastatin is a drug used as a first-line anti-cholesterol in the treatment of dyslipidemia. Low solubility will affect its ability to penetrate the digestive tract membrane and will affect the amount of drug levels in the plasma. The use of Cremophor-EL as a surfactant has been shown to inhibit the action of P-glycoprotein so that it can increase the bioavailability of a drug and can increase the effect of a drug. Methods: The preparation of simvastatin tablets was carried out using the wet granulation method. The dissolution test used the paddle method, a speed of 50 rpm at a temperature of 37±0.5 ° C with a phosphate buffer pH 7.0 as the dissolution medium. Results: The results showed that at 30 min the generic simvastatin tablets had 81.52% dissolution and the Simvastatin Tablets with Cremophor-EL were 85.520%. Conclusion: Simvastatin cremophor-EL tablets are more dissolved than generic simvastatin at 30 min so that cremophor-EL simvastatin tablets have a better dissolution rate than generic simvastatin tablets.

Improvement of Resveratrol Solubility by Complexation with Lactose Using Organic Solvent Spray Drying Technique

The purpose of this experiment is to change the crystallization state of resveratrol and improve its solubility and dissolution in water by spray drying technology, so as to improve the feasibility of resveratrol in clinical application. The powder samples were spray-dried with different proportions of ethanol aqueous solution as dissolution medium. The powder samples were characterized by infrared spectroscopy, thermogravimetry/differential scanning calorimetry, and ultraviolet spectroscopy, and their dissolution characteristics were investigated. It was found that the solubility and dissolution rate of different groups of samples obtained by spray drying increased compared with resveratrol crystals, and 50% ethanol solution had the greatest solubilization effect. The experimental results show that this method has a positive effect on the solubility of resveratrol and can regulate its dissolution behavior.

INHIBITION OF GASTRIC DEGRADATION OF OMEPRAZOLE USING A pH-SENSITIVE POLYMER AS A BINDER IN TABLET FORMULATION

Objective: This work was aimed at formulating omeprazole tablets using afzelia gum as a binder that is capable of inhibiting the gastric degradation of the drug. Methods: Afzelia gum at different concentrations of 0, 5, 10, 15, 20 and 30% was used as a binder to formulate omeprazole tablets. The tablets were formulated by direct compression and the batches labelled F1 to F6 respectively. A batch containing 15% hydroxypropyl methylcellulose (F7) was also formulated. The tablets were characterized; and dissolution in a pH 1.2 dissolution medium over 120 min period was studied. Aliquots taken every 20 min were analyzed by ultraviolet spectrophotometry to determine the amount of drug released and not degraded. Results: Amounts of drug released and not degraded at time 120 min were 53.1%, 57.3%, 57.8%, 58.8%, 62.1%, 83.4% and 90.0% for F1 to F7 respectively. Conclusion: Afzelia gum at a concentration of 30% is suitable for use as a binder in tablet formulation of omeprazole to ensure substantial inhibition of gastric degradation of the drug.

Development and Validation of RP-HPLC Chromatographic Dissolution Method for the Simultaneous Estimation of Ramipril and Hydrochlorothiazide from Solid Dosage Formulation

The present study describes the dissolution method development and validation of Ramipril and Hydrochlorothiazide in tablet dosage form by HPLC Method. A simple, rapid, selective, reproducible and isocratic reversed-phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated as per ICH guidelines. Analysis was performed on a Thermo, Sunniest C8 (150 mm x 4.6 mm, 5 µm) with the mobile phase consisting of mixing 500 mL of buffer solution and 500 mL of acetonitrile at a flow rate of 1.0mL/min. UV detection was performed at 210nm and the Run time for Ramipril and Hydrochlorothiazide were 10 minutes. The calibration curve was linear (correlation coefficient = 1.000) in the selected range for both analytes. The optimized dissolution conditions include the USP Type 1 (Basket) rotation rate of 100 rpm and 750 mL of 0.1 N Hydrochloric acid as dissolution medium, at 37.0 ± 0.5°C. The method was validated for precision, linearity, specificity, accuracy, limit of quantitation and ruggedness. The system suitability parameters, such as theoretical plate, tailing factor and relative standard deviation (RSD) between six standard replicates were well within the limits. The stability result shows that the drug is stable in the prescribed dissolution medium.

FORMULATION AND EVALUATION OF MELOXICAM MICROSPHERES FOR COLON TARGETED DRUG DELIVERY

Objectives: The objective of this research was to organize and evaluate colon specific microspheres of the meloxicam for the treatment of colorectal cancer. Methods: Sodium alginate microspheres were prepared by ionotropic gelation method using different ratios of meloxicam and sodium alginate (1:1, 1:2, and 1:3). Eudragit-coating of meloxicam, sodium alginate microspheres was performed by coacervation phase separation technique. Results: The microspheres were characterized by shape, particle size, size distribution, incorporation efficiency, in vitro drug release studies and stability studies. The outer surfaces of the core and coated microspheres, which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 20 to 52 μm, and therefore the size of the coated microspheres ranged from 107 to 178 μm. The core microspheres sustained the discharge for 10 h during a pH progression medium mimicking the condition of gastrointestinal tract. The release studies of coated microspheres were performed during a similar dissolution medium as mentioned above. In acidic medium the discharge rate was much slower, however the drug was released quickly at pH 7.4 and their release was sustained up to 24 h. Conclusions: It’s concluded from this investigation that Eudragit-coated sodium alginate microspheres are promising controlled release carriers for colon-targeted delivery of meloxicam.

Comparative studies of the kinetics of dissolution of medicines on the basis of clopidogrel

Generic medicines occupy dominant positions both in the pharmaceutical market of Ukraine and in industrial production by domestic pharmaceutical enterprises. The use of generic drugs in medical practice is of significant medical and social importance for expanding the accessibility of the general population to essential drugs. In Ukraine, more than twenty generic medicines based on clopidogrel, both foreign and domestic, are registered. All generic drugs containing clopidogrel bisulfate must comply with pharmaceutical bisulfate must comply with pharmaceutical equivalence, the kinetics of release of the active pharmaceutical ingredient using the Dissolution test in vitro, and pharmacokinetic parameters in vivo. The aim of the work was to carry out comparative studies of the dissolution kinetics of four samples of generic drugs based on clopidogrel with the dissolution kinetics of the original drug Plavix®, to evaluate the similarity factor of dissolution profiles and to determine the effect of biopharmaceutical factors on the equivalence of generics. Comparative studies of the kinetics of dissolution were carried out by the in vitro method according to the «Dissolution» test using a device with a blade with a rotation speed of 50 rpm, a dissolution medium with a pH value of 2.0 in a volume of 900 ml at a temperature of 37 ± 1 °C. The determination of the quantitative content of clopidogrel, which passed into the dissolution medium, was carried out by the method of adsorption spectrophotometry in the ultraviolet region at a wavelength of about 240 ± 2 nm. Based on the data obtained, the dissolution profiles of the original drug Plavix® and the studied samples of generic drugs were constructed, the similarity of which was assessed by the value of the similarity factor. According to the research results, it was found that one sample of the generic drug proved its equivalence by the in vitro method to Plavix®, and three other samples of generics had differences in dissolution kinetics in comparison with the original drug. Biopharmaceutical factors were analyzed that could affect the dissolution kinetics of the studied generic drugs, from which the physicochemical characteristics of clopidogrel bisulfate, the qualitative and quantitative composition of excipients and the features of the technological process were determined. Thus, on the basis of the comparative studies of the dissolution kinetics of drugs based on clopidogrel, generics were found that did not correspond to the in vitro equivalence according to the Dissolution test to the original drug, which could be due to the influence of a combination of biopharmaceutical factors.

COMPARATIVE DISSOLUTION STUDIES OF WARFARIN SODIUM TABLETS: INFLUENCE OF AGITATION RATE, DISSOLUTION MEDIUM, AND USP APPARATUS

Objective: The aim of this study was to carry out comparative dissolution studies with warfarin sodium reference tablets under the hydrodynamic environments generated by the USP basket and paddle apparatus and flow-through cell using different agitation rates and dissolution media. Methods: Dissolution profiles were obtained with the USP basket and paddle apparatus at 50, 75, and 100 rpm and 900 ml of water as dissolution medium. After this, dissolution profiles of warfarin sodium were obtained with the USP paddle apparatus and flow-through cell method using 0.1 N hydrochloric acid, acetate buffer pH 4.5, phosphate buffer pH 6.8, and water. Spectrophotometric determination at 308 nm was carried out during 30 min. Dissolution profiles were compared with model-independent and model-dependent approaches. Results: Significant differences were found with mean dissolution time and dissolution efficiency at 50 and 75 rpm (*P<0.05). Makoid-Banakar was the best-fit model used to describe the in vitro release performance of warfarin sodium with 50-100 rpm and the USP basket and paddle apparatuses. Significant differences in all calculated parameters were found (*P<0.05) excepting percent dissolved at 30 min with 0.1 N hydrochloric acid and phosphate buffer pH 6.8. Conclusion: More research is necessary to identify the in vitro release performance of poorly soluble drugs under available USP apparatuses considering factors as agitation rate and kind of dissolution media. The knowledge of the in vitro release performance of reference drug products is important for the design of better generic formulations

DISSOLUTION PROFILE OF METRONIDAZOLE TABLET IN DIVERSE FATTY MEDIUMS

The aim of the study was to confirm the interaction of food with metronidazole 400 mg tablet with diverse dissolution medium like milk, oil and gastric fluid to observe the effects of physiological changes in terms of absorbance.