A Promising Single Oral Disintegrating Tablet for Co-Delivery of Pitavastatin Calcium and Lornoxicam Using Co-Processed Excipients: Formulation, Characterization and Pharmacokinetic Study

• Published in: Drug design, development and therapy development and therapy, 2021-01, Vol.15, p.4229-4242
• Main Authors: Teaima, Mahmoud H, Abdel-Haleem, Khaled M, Osama, Rewan, El-Nabarawi, Mohamed A, Elnahas, Osama S
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animal models; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Bioavailability; Biological Availability; Calcium; Chemistry, Pharmaceutical - methods; Chromatography, Liquid; co-processed excipients; Compression; Compression tests; Disintegration; Drug Combinations; Drug delivery; Drug Delivery Systems; Drug Liberation; Drugs; Excipients; Excipients - chemistry; Fourier transforms; Friability; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - chemistry; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Hyperlipidemia; in-vivo pharmacokinetic study; Inflammation; Liquid chromatography; liquid chromatography-mass spectrometry; lornoxicam; Male; Mass spectrometry; Mass spectroscopy; Myopathy; Nonsteroidal anti-inflammatory drugs; oral disintegrating tablets; Original Research; Parameters; Patient compliance; Pharmaceutical industry; Pharmacokinetics; Pharmacology; Physical properties; Piroxicam - administration & dosage; Piroxicam - analogs & derivatives; Piroxicam - chemistry; Piroxicam - pharmacokinetics; pitavastatin calcium; Potassium; Quinolines - administration & dosage; Quinolines - chemistry; Quinolines - pharmacokinetics; Rats; Rats, Wistar; Solubility; Statins; Tablets; Tandem Mass Spectrometry; Variance analysis; Wetting
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S332729

Statins are an important class of drugs that help to control hyperlipidemia, and one of these statins recently used is pitavastatin calcium (PITA). Nevertheless, the most reported adverse effect of statins is myopathy. Therefore, combining statins with non-steroidal anti-inflammatory drugs (NSAIDs) as Lornoxicam (LORNO) can help in the management of statin-induced myopathy. This study aimed to formulate and evaluate different oral disintegrating tablets (ODTs) containing PITA using different co-processed excipients. The best PITA-ODT was selected and reformulated with the addition of LORNO, forming a single ODT comprising both drugs. The pharmacokinetic parameters of PITA and LORNO in a single ODT were compared to those of the marketed products (Lipidalon and Lornoxicam ). Eight PITA-ODTs were prepared via direct compression. The prepared PITA-ODTs were evaluated for their weight variation, thickness, breaking force, friability, drug content, and wetting time (WT). In-vitro disintegration time (DT) and dissolution were also evaluated and taken as parameters for selection of the best formula based on the criteria of scoring the fastest DT and highest Q . LORNO was added to the selected PITA-ODT, forming a single ODT (M1) comprising both drugs, which was subjected to an in-vivo pharmacokinetic study using rats as an animal model and liquid chromatography-mass spectrometry (LC-MS/MS) for analysis of both drugs in rat plasma. Results showed that all PITA-ODTs had acceptable physical properties in accordance with pharmacospecial standards. PITA-ODT prepared with Pharmaburst (F2) had significantly (