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

Significance: 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.

Purpose: 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^®).

Methods: 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_{10 min}. 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: Results showed that all PITA-ODTs had acceptable physical properties in accordance with pharmacospecial standards. PITA-ODT prepared with Pharmaburst^® (F2) had significantly (p< 0.05) the fastest DT (6.66± 1.52 s) and highest Q_{10 min} (79.07± 2.02%) and was chosen as the best formula. The in-vivo pharmacokinetic study of M1 formula showed higher percent relative bioavailability (%RB) of 286.7% and 169.73% for PITA and LORNO, respectively, compared with the marketed products.

Conclusion: The single ODT comprising PITA and LORNO was promising for instant co-delivery of both drugs with higher %RB when compared with the marketed products.

Materials

Pitavastatin calcium (PITA) and Lipidalon^® tablets (1 mg) were a kind gift sample from Mash Premiere for Pharmaceutical Industry (New Cairo, Egypt). Lornoxicam (form II) (LORNO) and Lornoxicam^® tablets (4 mg) were obtained as a gift sample from Global Napi drug company Ltd (6th October City, Egypt). Pharmaburst^® 500 and Lubripharm^® Ssf (sodium stearyl fumarate) were a gift from SPI Pharma (Wilmington, DE, USA). F-melt^® Type C was provided by Fuji Chemical Industry Ltd. (Toyama-Pref, Japan). Prosolv ODT G2^® and Prosolv HD 90^® were a gift from JRS Pharma GmbH and Co., KG (Rosenberg, Germany). Ludiflash^® was provided by BASF (Ludwigshafen, Germany). Lactochem^® Microfine was a gift sample from (Borculo Domo, Netherlands). Starlac^® and Pearlitol flash^® were obtained from Roquette (Lestrem, France). Mannitol, potassium dihydrogen phosphate, and disodium hydrogen phosphate were purchased from (El-Nasr Pharmaceutical Chemicals Co., Cairo, Egypt). Diethyl ether was from (El-Goumhouria Co., Cairo, Egypt). Torsemide (internal standard) was purchased from (Multi-Apex Pharma, Cairo, Egypt). Acetonitrile, ammonium acetate, and ethyl acetate (HPLC grade) were from Merck (Darmstadt, Germany)

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Teaima MH, Abdel-Haleem KM, Osama R, El-Nabarawi MA, Elnahas OS. A Promising Single Oral Disintegrating Tablet for Co-Delivery of Pitavastatin Calcium and Lornoxicam Using Co-Processed Excipients: Formulation, Characterization and Pharmacokinetic Study. Drug Des Devel Ther. 2021;15:4229-4242
https://doi.org/10.2147/DDDT.S332729