Formulation and evaluation of dexlansoprazole extended-release tablet

Dexlansoprazole (DSP) is a proton pump inhibitor, it used to treat GERD and ulcer colitis. DSP works by decreasing the volume of acid in the stomach. DSP is an acid-labile medication that may be destroyed in the stomach's acidic pH. A coating technique was used to postpone drug release in the stomach, which can extend pharmacological activity. Shellac can be used to develop the sustain release tablet of dexlansoprazole as retardation of the drug (dexlansoprazole) was observed in the acidic pH of the stomach, and hence a sustain coated dexlansoprazole tablet was prepared and evaluated. The coating's primary function is to allow for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits faster degradation in the acidic pH of the stomach, therefore increasing pharmacological action. DSP coating with different polymers inhibits fast degradation in the stomach's acidic pH, enhancing pharmacological action. The major function of the coating is to enable for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits fast breakdown in the stomach's acidic pH, enhancing pharmacological action.

Formulation and Evaluation of Cefaclor Extended-Release Tablet

Over past 30 years as the expanse and complication involved in marketing new drug entities have increased, with concomitant recognition of the therapeutic advantages of controlled drug delivery, greater attention has been focused on development of extended or controlled release drug delivery systems. In the present research work an attempt has been made to optimize, formulate and characterize extended-release tablet of Cefaclor. The preformulation studies were performed for the drug (e.g., physico-chemical properties, melting point, solubility etc.). The drug had shown the results under standard specifications. UV spectroscopic analytical method was also performed for quantitative determinations by plotting standard curve. Before this the pure drug was also scanned for the ƛ max value at different concentrations. The pre-compressions parameters and the post compression parameters for the nine formulated tablets were performed. The drug release study of the selected formulations EF3, EF6 and EF9 was performed as those formulations has shown the results within pharmacopoeia limits. The Formulation EF9 was then taken for release kinetic study as it has shown best results among the other three formulations. So, it confirms the drug release by Higuchi diffusion mechanism. From the results, conclusion can be drawn that the formulation consisting 10-12% concentration of hydroxypropyl methyl cellulose K4-M with 1% microcrystalline cellulose and 25% of lactose are considered as ideal for the optimized extended-release tablet formulation for Cefaclor. Keywords: Extended release, Cefaclor, Higuchi diffusion mechanism, PBP, bacterial cell wall synthesis.

FORMULATION AND OPTIMIZATION OF NATURAL GUM BASED EXTENDED RELEASE TABLETS OF LOSARTAN USING D-OPTIMAL MIXTURE DESIGN

Objective: Losartan potassium is one of the widely prescribed antihypertensive drugs administered orally and its extended-release tablet formulations are essentially required for the long-acting effect at reduced dosage frequency. The present research was aimed for the development and optimization of an extended-release tablet of losartan potassium, exploring natural gums, i.e., xanthan gum and guar gum as drug release modifiers. Methods: The tablet formulation was prepared by wet granulation method and the formulation optimization was done by D-optimal mixture design using Design Expert® software. The independent variables studied were xanthan gum (X1), guar gum (X2) and lactose (X3) taking various combinations of the total amount of gum and ratio of xanthan gum to guar gum under the given constraint range. The dependent (response) variables studied were % drug release in 1h (Y1), 4h (Y2), 7h (Y3) and 10h (Y4). The developed tablets were evaluated for physical properties, i.e., hardness, friability, weight variation as well as the in vitro drug release profiles. For optimization studies, the polynomial equations and response surface plots were generated and the optimized formulation was selected on the basis of maximum desirability value. Results: The developed tablet formulation was found to possess all physical properties within the desired range and showed sustained release profile with ~80% drug release in 10 h duration. The model fitting studies demonstrated best fit in the zero-order model and the slope value of Korsmeyer–Peppas plot was ˃0.89, suggesting case II transport as a drug release mechanism. Conclusion: The findings suggested that natural gums-based matrix tablets of losartan could be successfully developed and natural gums can be explored as platform technology as release retardants and in the development of sustained-release matrix tablets of other drugs.

Formulation of Extended-Release Ranolazine Tablet and Investigation Its Stability in the Accelerated Stability Condition At 40⁰C And 75 % Humidity

Formulation of Ranolazine in the form of extended-release tablet in 500 mg dosage form was performed using Eudragit L100-55 as a retarding agent. Drugrelease profiles were investigated in comparison with the reference Ranexa extended-release 500 mg tablet. F2 and f1 were calculated as 64.16 and 8.53, respectively. According to Peppas equation, the release of drug is controlled by diffusion (n=0.5). The tablets were put into accelerated stability condition (40⁰C, 75% humidity) for 3 and 6 months. The dissolution release profiles and other physical and chemical characteristics of the tablets confirmed the robustness and stability of formulation in this condition.

AB1305-HPR IS BETTER AND SAFER TOFACITINIB AS A FIRST LINE OF TREATMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS? – A COHORT STUDY

Background:Tofacitinib is the first oral Janus Kinasa inhibitor approved for the treatment of rheumatoid arthritis (RA); and although it is approved both after conventional treatment and after biological therapy, it is not well known its real-life effectiveness in both cases and if it is preferable to use it after cDMARDs or biologics.Objectives:We compare the effectiveness and safety of Tofacitinib in patients with RA analyzing if better and safer Tofacitinib after cDMARDs or biologics.Methods:A retrospective analysis of a real-world cohort of patients with RA, who were treated with Tofacitinib in last 3 years, as first line of treatment (T1) after failure with cDMARDS and second line of treatment after biologic drug failure (T2). The therapy was considered effective with the change from moderate-high disease activity to low disease activity or remission measured by DAS28, in those who met criteria of high adherence, without change or addition of other conventional DMARDs, without new dose or increase of dose of oral glucocorticoids. A logistic model of regression was performed to evaluate de differences between T1 and T2, using as covariates sex, age, comorbidities, time of disease evolution, adverse events and other causes of discontinuation. Medication survival time and the main causes of suspension were measured. Mixed model regression and least-squared means were used to estimate the baseline changes and a Kaplan-Meyer survival analysis to estimate time to remission and drug survival.Results:105 patients with RA were included (median age: 56.1 ± 11.7 years; 80.9% female, median disease duration 11.48 ± 10.1 years); 43% (45/105) of patients with positive rheumatoid factor and 73% (77/105) positive anti-citrulline antibodies. Regarding treatment 51% (54/105) used Tofacitinib as 1T, after failure to cDMARDs; on the other hand, Tofacitinib was used as 2T, after failure to biologics in 49% (51/105) of patients. DAS28 levels were reduced at 8, 16 and 24 weeks with statistical difference (p value 0.004, <0.0001, and <0.001, respectively). HAQ-DI also reported reduction but without statistical difference. The use of Tofacitinib was more effective after failure to cDMARDs (p value 0.014) and patients with more than 3 years of disease (p value 0.04), a statistically better response. Also, corticoids use, positive RF, extended release tablet of tofacitinib reported better changes of DAS28 but without statistical significance. Patients with high disease activity treated with Tofacitinib 1T decreased from 30% at baseline to 19% at the last follow-up; patients in 2T way were in moderate activity of the disease in 57% at baseline and went to 37% in the last follow-up. There was an increase in patients who achieved remission in both groups, but higher in 1T where they went from 9% to 41%, while in 2T they went from 22% to 33% (p < 0.05). The survival rate of the medication was 1.7 years in 1T and 2.1 in 2T; in terms of time to remission, the use of Tofacitinib monotherapy presented statistical difference (p value <0.001). The main cause of suspension of treatment was therapeutic failure 12% (13/105), 9% in 1T (5/54) and 16% (8/51) in 2T (p <0.005). 6% of patients (6/105) presented suspension due to the occurrence of adverse events, 4% (2/54) in 1T and 8% (4/51) in 2T (p <0.005).Conclusion:In patients with RA, the use of Tofacitinib as the first line of treatment (after failure to cDMARDs) is better in effectiveness and safer in comparison with its use as a second line of treatment (after biologics), with significant differences in the rates of therapeutic failure and occurrence of adverse events/reactions. On the other hand, concomitant corticoids use, positive RF, extended release tablet of Tofacitinib seem to increase the effectiveness of Tofacitinib in terms of DAS28 and HAQ-DI.Disclosure of Interests:Omaira Valencia: None declared, Michael Cabrera: None declared, Fernando Rodriguez: None declared, Pedro Santos-Moreno Grant/research support from: I have received research grants from Abbvie, Biopas-UCB, Janssen, Novartis, Pfizer., Speakers bureau: I have been a speaker for Abbvie, Biopas-UCB, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi.