Study of the dissolution kinetics of drugs in solid dosage form with lisinopril and atorvastatin and intestinal permeability to assess their equivalence in vitro

Atorvastatin and lisinopril are a successful combination for the treatment of patients with chronic heart failure and hypertension. Study of the dissolution kinetics of drugs in solid dosage form with lisinopril and atorvastatin and intestinal permeability to assess their equivalence in vitro were described. In medium with hydrochloric acid pH 1.2, in the medium of acetate buffer solution with a pH of 4.5 and in the medium phosphate buffer solution with a pH of 6.8 for 15 min more than 85% of the active substance passes into solution, hence the dissolution profiles these drugs in these environments are similar, and the drugs in them are “very quickly soluble”. Among the in vitro models that make it possible to assess the degree of absorption of API, the most widely used culture of adenocarcinoma cells of the colon – Caco-2. The development of the analytical methodology and its validation is the final stage of both the dissolution study and the Caco-2 test, as well as the biowaver procedure. It plays the most important role in the reliability of the results for all the above procedures and tests. To study permeability, method LC-MS/MS was developed. According to the obtained results, atorvastatin and lisinopril showed low permeability. The values ​​of recovery of transport of test and control substances through the monolayer of cells of the Caco-2 line indicate that the results of the experiment can be considered reliable. The equivalence of the drugs “Lisinopril”, tablets of 10 mg and “Atorvastatin”, tablets of 10 mg, belongs to class III BCS proven by in vitro studies.

PHARMACEUTICAL STANDARDIZATION OF AGNIKUMARA RAS

Bhaishajya Kalpana is an integral part of Ayurveda which deals with the process of preparation of single and com- pound formulations. The preparation of drugs can be classified into two groups, primary and secondary. Vati is a popular secondary preparation in Ayurvedic pharmaceutics. It is a solid dosage form that is produced and marketed in the field of pharmaceutics. This is because of the advantages like it can be swallowed easily without any irritation, handy and fixation of dosage becomes easier. Agnikumara Ras is one such formulation mentioned in Basava- rajeeyam pradhama prakarana indicated in Peenasa, Jwara, ama and Pratishyaya. Agnikumara ras contains Shud- dha Vatsanabha, Maricha, Mustha, Kushta and Vacha. The pharmaceutical procedures adopted in this study are Shodana, Churna nirmana, mardana and preparation of vati of Agnikumara ras. Till now, no research work has been carried out to standardize the method of preparation Agnikumara Ras. Therefore, the present study has been planned to standardize the method of preparation of Agnikumara ras according to the method explained in the classics. Keywords: Agnikumara ras, Shodana, Churna nirmana, pharmaceutical standardization.

A NEW ROBUST ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF RIBOCICLIB AND LETROZOLE IN SOLID DOSAGE FORM (TABLET)

Objective: The objective of the study was to develop a new robust, sensitive, precise, accurate RP-HPLC analytical method and validate for simultaneous estimation of ribociclib and letrozole in solid dosage form (tablet). Methods: The chromatographic separation was carried out on Waters, symmetry C18 (150 mm×4.6 mm with 3.5 μm), mobile phase used was a mixture of buffer and acetonitrile in the ratio of 80:20, with flow rate of 1ml/min and injection volume of 10 μL for the assay. The detection was done using PDA at 260 nm, with run time of 5 min. The retention time for the drugs ribociclib and letrozole was detected to be 2.648 min and 3.151 min, respectively. The method was validated according to ICH guidelines. Results: The linearity of letrozole and ribociclib was observed to be in the range of 0.50–7.50 and 40.01–600.15, Correlation coefficient (r2) 0.999 and 0.9983, respectively. Accuracy for ribociclib and letrozole is carried out by repeatable concentrations of 50%, 100%, and 150. Validation factors of robustness and ruggedness were detected to be in limits. Conclusion: The developed method was simple, rapid, and consistent; it can be used for the simultaneous estimation of ribociclib and letrozole tablet dosage form in routine analysis.

Modelling and Simulation of the Drug Release from a Solid Dosage Form in the Human Ascending Colon: The Influence of Different Motility Patterns and Fluid Viscosities

For colonic drug delivery, the ascending part of the colon is the most favourable site as it offers the most suitable environmental conditions for drug dissolution. Commonly, the performance of a drug formulation is assessed using standardised dissolution apparatus, which does not replicate the hydrodynamics and shear stress evoked by wall motion in the colon. In this work, computer simulations are used to analyse and understand the influence of different biorelevant motility patterns on the disintegration/drug release of a solid dosage form (tablet) under different fluid conditions (viscosities) to mimic the ascending colonic environment. Furthermore, the ability of the motility pattern to distribute the drug in the ascending colon luminal environment is analysed to provide data for a spatiotemporal concentration profile. The motility patterns used are derived from in vivo data representing different motility patterns in the human ascending colon. The applied motility patterns show considerable differences in the drug release rate from the tablet, as well as in the ability to distribute the drug along the colon. The drug dissolution/disintegration process from a solid dosage form is primarily influenced by the hydrodynamic and shear stress it experiences, i.e., a combination of motility pattern and fluid viscosity. Reduced fluid motion leads to a more pronounced influence of diffusion in the tablet dissolution process. The motility pattern that provoked frequent single shear stress peaks seemed to be more effective in achieving a higher drug release rate. The ability to simulate drug release profiles under biorelevant colonic environmental conditions provides valuable feedback to better understand the drug formulation and how this can be optimised to ensure that the drug is present in the desired concentration within the ascending colon.

In-Vitro Functionality of Clozapine Biphasic Release Minitablet Using Advanced Statistical Tools

Background: The better control of the drug release with immediate effect is the major concern to achieve better therapeutic action and patient compliance. The failure of the solid dispersion complex during storage as well as in-vivo is another concern for the oral solid dosage form. Objective: The prime objective of the present study was to optimize the biphasic minitablet incorporating quality by design approach using the combination of waxy erodible and water-impermeable excipients. Exploration of Soluplus as a precipitation inhibitor and Dexolve as a solubility enhancer in oral solid dosage form was the secondary objective. Methods: The drug-Excipient compatibility study was assessed by FTIR. Clozapine was chosen as a model drug that has poor aqueous solubility. The complex was formulated using B-cyclodextrin or HP B-CD or Dexolve by kneading method. The screening of solubility enhancers and their amount were performed based on phase solubility study. The precipitation inhibitor was screened as per the parachute effect study. Immediate release minitablets were formulated using a direct compression method using different disintegrating agents. The IR minitablets were evaluated for different evaluation parameters. The sustained release minitablets was formulated by hot-melt granulation technique incorporating the Precirol ATO 5 as a waxy excipient and ethyl cellulose as water impermeable excipient. The SR minitablet was optimized using a central composite design. The amount of Precirol ATO 5 and ethyl cellulose were chosen as independent variables and % drug release at 1, 6, and 10 h was selected as responses. The designed batches were evaluated for different pre and post compressional parameters. The IR and SR minitablets were filled in a capsule as per dose requirement and evaluated for in-vitro drug release. The in-vivo plasma concentration was predicted using the Back calculation of the Wagner – Nelson approach. Results: Drug – Excipient study revealed that no significant interaction was observed. Dexolve was screened as a solubility enhancer for the improvement of the solubility of clozapine. The Soluplus was chosen as a precipitation inhibitor from the parachute effect study. The immediate-release tablet was formulated using Prosolv EASYtab SP yield less disintegration time with better flowability. The sustained release mini-tablet was formulated using Precirol ATO 5 and ethyl cellulose. Two-dimensional and three-dimensional plots were revealed the significant effect of the amount of Precirol ATO 5 and ethyl cellulose. The overlay plot locates the optimized region. The in-vitro drug release study revealed the desired drug release of the final combined formulation. The in-vivo plasma concentration-time confirms the drug release up to 12h. Conclusion: The biphasic mini-tablets were formulated successfully for better control of drug release leads to high patient compliance. The use of soluplus as a precipitation inhibitor is explored in the oral solid dosage form for a poorly aqueous drug. Prosolv EASYtab SP was incorporated in the formulation as super disintegrant. The amount of Precirol ATO 5 and ethyl cellulose had a significant effect on drug release in sustained-release minitablet. The approach can be useful in the industry.