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.

941. Isavuconazole Prophylaxis Against Invasive Fungal Infection: A Pooled Analysis with a Comparison of Posaconazole Delayed-release Tablet Prophylaxis

Background There are limited data regarding the use of isavuconazole as primary antifungal prophylaxis against invasive fungal infection (IFI) among immunocompromised patients. Therefore, the purpose of this study was to assess efficacy and breakthrough IFIs of isavuconazole prophylaxis by a pooled analysis of the reported cases of isavuconazole prophylaxis with a comparison of cases of posaconazole delayed-release tablet prophylaxis. Methods Pubmed was searched for English-written articles published up to April 2021. Studies that reported cases of primary antifungal prophylaxis with isavuconazole or posaconazole delayed-release tablet in adults ≥ 18 years were reviewed. Breakthrough IFI was defined as the occurrence of proven or probable IFI while on prophylaxis. Results For overall isavuconazole prophylaxis, a total of 818 courses of prophylaxis was identified from 12 studies. Breakthrough IFIs were noted in 41 patients. The median duration of isavuconazole prophylaxis of these patients before the diagnosis of IFI was 17 days. The most common breakthrough IFI was candidiasis (34.1%), followed by aspergillosis (24.4%) and mucormycosis (12.2%). Sixteen patients died (39.0%). Among patients with hematologic malignancies or hematopoietic stem cell transplantation, isavuconazole prophylaxis (404 courses) was compared with posaconazole delayed-release tablet prophylaxis (1952 courses). The incidence rate of breakthrough IFIs was higher in the cohort of isavuconazole prophylaxis (24 patients of 404 courses) than in the cohort of posaconazole delayed-release tablet prophylaxis (44 patients of 1952 courses). Aspergillosis (40.9%) was the most common breakthrough IFI in the cohort of isavuconazole prophylaxis among patients with hematologic malignancies or hematopoietic stem cell transplantation, followed by candidiasis (27.3%) and mucormycosis (18.2%). Conclusion Although isavuconazole is licensed to treat aspergillosis and mucormycosis, breakthrough IFIs including aspergillosis, mucormycosis, and candidiasis may occur while on isavuconazole prophylaxis. Therefore, further studies are needed to define the benefits and risks of isavuconazole prophylaxis. Disclosures All Authors: No reported disclosures

Formulation and Development of Metoprolol Succinate Sustained Release Matrix tablet using Remusatia vivipara tubers mucilage

The purpose of this research was to formulate and evaluate sustained release tablet by using novel polymer Remusatia vivipara tubers mucilage. Currently natural gums and mucilages are being used extensively comparable to synthetic drug release modifiers. Natural plant materials possess various advantages. These are very cheap, biocompatible, biodegradable and free from side effects. In present research Metoprolol succinate matrix tablets were prepared by using Remusatia vivipara tubers mucilage. For the formulation of sustained release matrix tablets, direct compression method was used. The formulated matrix tablets were then evaluated for thickness, diameter, hardness, weight variation, friability, drug content, swelling index, in-vitro drug release and stability studies. The formulated sustained release tablet passed all tests required. The dissolution profile of prepared tablets showed sustained release of drug up to 11 hours compared to the reference tablet formulation PROLOMET XI 100. Drug release data were then fitted in to release kinetic models such as zero order kinetic, first order kinetic, Higuchi model and Korsmeyer-Peppas model to study the release pattern of drug from each formulation. The prepared sustained release tablet formulation was compared with marketed formulation (reference formulation) for drug release study and factor f1 (difference factor) and f2 (similarity factor) were determined. From this study it can be concluded that as the concentration of Remusatia vivipara mucilage increases, there is decrease in the rate of drug release from the formulation. The best formulation was found to be F3 which consists of 20% Remusatia vivipara mucilage but did not give comparable drug release profile to the reference formulation with factor f1 69.4 % and f2 34.8%. But it can be said that Remusatia vivipara gum mucilage can be used in tablet formulation to give sustained release effect up to 10 hours or in combination with other natural gum mucilage it may enhance the release retardant effect of drug up to or more than 20 hrs. The release kinetic study showed that the prepared sustained release tablet formulation shows anomalous (non-fickian) diffusion pattern and follows both diffusion controlled and swelling controlled mechanisms for drug release.

Increased Bioavailability of β-Alanine by a Novel Controlled-Release Powder Blend Compared to a Slow-Release Tablet

Background: β-Alanine is a sport supplement with increasing popularity due to its consistent ability to improve physical performance, with the downside of requiring several weeks of supplementation as imposed to the maximum daily and single dose tolerated without side effects (i.e., paresthesia). To date, the only alternative to overcome this problem has been use of a sustained-release tablet, while powders are the most commonly used format to deliver several grams of amino acids in a single dose. In this study we assessed the bioavailability, pharmacokinetics and paresthesia effect of β-alanine after administration in a novel controlled-released powder blend (test) versus a sustained-release tablet (reference). Methods: Twelve subjects (25.6 ± 3.2 y, 50% female) participated in a randomized, single-blind, crossover study. Each participant was administered orally the test (β-alanine 8 g, l-histidine 300 mg, carnosine 100 mg) or the reference product (10 tablets to reach β-alanine 8 g, Zinc 20 mg) with a 1-week washout period. β-Alanine plasma concentrations (0–8 h) were determined by LC-MS/MS and model-independent pharmacokinetic analysis was carried out. Paresthesia intensity was evaluated using a Visual Analog Score (VAS) and the categorical Intensity Sensory Score (ISS). Results: The CMAX and AUC0→∞ increased 1.6- and 2.1-fold (both p < 0.001) in the test product, respectively, which yielded 2.1-fold higher bioavailability; Ka decreased in the test (0.0199 ± 0.0107 min−1) versus the reference (0.0299 ± 0.0121 min−1) product (p = 0.0834) as well as V/F and Cl/F (both p < 0.001); MRT0→last increased in the test (143 ± 19 min) versus reference (128 ± 16 min) formulation (p = 0.0449); t1/2 remained similar (test: 63.5 ± 8.7 min, reference: 68.9 ± 9.8 min). Paresthesia EMAX increased 1.7-fold using the VAS (p = 0.086) and the ISS (p = 0.009). AUEC increased 1.9-fold with the VAS (p = 0.107) and the ISS (p = 0.019) reflecting scale intrinsic differences. Pharmacokinetic-pharmacodynamic analysis showed a clockwise hysteresis loop without prediction ability between CMAX, AUC0→∞ and EMAX or AUEC. No side effects were reported (except paresthesia). Conclusions: The novel controlled-release powder blend shows 100% higher bioavailability of β-alanine, opening a new paradigm that shifts from chronic to short or mid-term supplementation strategies to increase carnosine stores in sports nutrition.

Formulation and Evaluation of Effects of Superdisintegrants on Immediate Release Tablet of Linagliptin, a DDP-4 Inhibitor

The study aimed to develop and evaluate an immediate-release tablet dosage form of Linagliptin. Different concentrations (ranges 5-10%) of super-disintegrants, Croscarmellose sodium (CCS), and Sodium starch glycolate (SSG) were used to prepare nine tablet dosage forms (F1 to F9) through the direct compression method. The compatibility of the formulations was evaluated by FTIR to reveal any possible drug-excipient interactions and it was proved to be compatible with all formulations. Precompression (bulk density, tapped density, Carr’s index, Hausner’s ratio, and angle of repose) and post-compression parameters (weight variation, hardness, thickness, and friability) were analyzed for all tablets and the results were found satisfactory as well as within limits as per USP guidelines. All the formulated batches (F1 to F9) exhibited disintegration of tablets within 2 minutes, where formulation F9 represented the lowest disintegration time (51±3 sec) which was also found significantly better than the marketed product (310±5 sec). In terms of drug dissolution, 90% of drug release was observed for all nine formulations within 45 minutes and formulation F9 (5% CCS and 5% SSG) illustrated the rapid and highest dissolution rate compared to the marketed one’s, 100% drug release at 20 minutes and 91.77 % drug release at 30 minutes successively. The respective data sets of drug release were mathematically fitted to several kinetic models and for all formulations, drug release pattern obeyed first-order kinetics amongst those, formulation F2 (r2= 0.98), F4 (r2= 0.99), F5 (r2= 0.98), and F9 (r2= 0.97) were found to be best fitted in this kinetic norm. Based on disintegration time and dissolution data comparison to a brand leader market product, F9 was experienced as the best formulation. Furthermore, it was observed that if SSG and CCS were combined, then these two parameters were more improved compared to their separate uses. Thus, incorporation of the optimum amount of super-disintegrants in a formulation showed rapid swelling, faster disintegration as well as ease of dissolution of tablet dosage forms. Bangladesh Pharmaceutical Journal 24(2): 168-179, 2021