Directly compressed rosuvastatin calcium tablets that offer hydrotropic and micellar solubilization for improved dissolution rate and extent of drug release

Abstract

The objective was to use caffeine and Soluplus® to improve the dissolution rate and to maintain a concentration of BCS Class II rosuvastatin calcium that exceeds its solubility. Caffeine and Soluplus® together substantially improved the dissolution rate and the extent of rosuvastatin release. Formulations for direct compression tablets included Formulation F1, a control with drug but with neither caffeine nor Soluplus® present; F2 with drug-caffeine complex; F3 with drug and Soluplus® and F4 with drug-caffeine complex and Soluplus®. Each formulation blend provided satisfactory flow properties. Tablets were comparable in mass, hardness and friability. A marked decrease in disintegration time occurred when the hydrotropic or micellar agent was included in the formulation. Assay (98–100%) and content uniformity (99–100%) results met requirements. Release studies in pH 1.2, 6.6, and 6.8 buffers revealed the superiority of F4. At 45 min sampling time, F3 and F4 tablets each provided a cumulative drug release greater than 70% in each medium. F2 tablets exhibited compliance to official standards in pH 6.6 and 6.8 buffers but not in pH 1.2 buffer, whereas tablets based on F1 failed in each medium. Two-factor ANOVA of the release data revealed a statistical difference across the four formulations in each release medium. Pairwise comparison of release profiles demonstrated that, of the four formulations, F4 provided the most effectively enhanced dissolution rate, improvement to the extent of drug release and support of a concentration higher than the solubility of rosuvastatin calcium.

Development of Multi-Compartment 3D-Printed Tablets Loaded with Self-Nanoemulsified Formulations of Various Drugs: A New Strategy for Personalized Medicine

“…GLMP has a biological half-life of approximately 5 h. RSV is the most potent and widely prescribed statin member that decreases low-density lipoprotein cholesterol and is therefore prescribed to prevent cardiovascular disorders [ 22 ]. RSV is characterized by its limited solubility in the gastrointestinal fluids and is subjected to extensive first-pass metabolism, the effects that result in a limited drug oral bioavailability (approximately 20%) [ 23 , 24 ]. To manage dyslipidemia in diabetic patients, both drugs (GLMP and RSV) should be administered concomitantly [ 20 ].…”

Development of rosuvastatin flexible lipid-based nanoparticles: promising nanocarriers for improving intestinal cells cytotoxicity

“…Similar to other statins, the mechanism of action of RSV is attributed to competitive inhibition of the enzyme 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase [30]. RSV has a low water solubility and exhibits a limited solubility in the gastrointestinal fluids [11]. The drug is subjected to extensive first pass metabolism after oral administration.…”

Pengaruh Pengembangan Self-Nanoemulsifying Drug Delivery System Terhadap Disolusi, Bioavailabilitas, Dan Aktivitas Agen Antihiperlipidemia

“…Beberapa kelompok agen hiperlipidemia ini memiliki hambatan pada pemberian oral, berkaitan dengan sifat fisikokimianya. Agen antihiperlipidemia seperti simvastatin (Jiang et al, 2012), rosuvastatin calsium (Butt et al, 2019), atorvastatin (Prabhu & Patravale, 2016, gemfibrozil (Reddy et al, 2011) termasuk ke dalam kelompok BCS (biopharmaceutical classification system) kelas II dengan kelarutan yang rendah dalam air dan permeabilitas yang baik (Van Den Abeele et al, 2016). Beberapa modifikasi formulasi banyak dilakukan untuk memperbaiki kelarutan dan bioavaibilitas dari senyawa-senyawa tersebut salah satunya dengan mengembangkan bentuk SNEDDS (selfnanoemulsifying drug delivery system) (Elgart et al, 2013).…”