Tolmetin Sodium Fast Dissolving Tablets for Rheumatoid Arthritis Treatment: Preparation and Optimization Using Box-Behnken Design and Response Surface Methodology

Pharmaceutics

卷:14

Bakheet E. M. Elsadek¹  Moustafa O. Aboelez²  Eslam B. Elkaeed³  Mahmoud M. A. Elsayed⁴  Amany A. Abdel-Rheem⁴  Ahmed Khames⁵  Mahmoud Elkot Mostafa Elsadek⁶  Yasser A. Hassan⁷  Khaled Ali Khaled⁸  Hatem A. Sarhan⁸  Mohamed Raafat⁹  Amany Belal¹⁰ 

[1] Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Cairo 11371, Egypt;

[2] Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt;

[3] Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia;

[4] Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt;

[5] Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, Taif 21944, Saudi Arabia;

[6] Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Merit University, Sohag 82755, Egypt;

[7] Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt;

[8] Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;

[9] Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia;

[10] Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;

关键词: fast disintegrating tablets;    tolmetin sodium;    response surface methodology;    Box-Behnken experimental design;   

DOI  :  10.3390/pharmaceutics14040880

来源: DOAJ

【 摘 要 】

Tolmetin sodium (TLM) is a non-steroidal anti-inflammatory drug (NSAIDs). TLM is used to treat inflammation, skeletal muscle injuries, and discomfort associated with bone disorders. Because of the delayed absorption from the gastro intestinal tract (GIT), the currently available TLM dosage forms have a rather protracted start to the effect, according to pharmacokinetic studies. The aim of this study was to create a combination for TLM fast dissolving tablets (TLM-FDT) that would boost the drug’s bioavailability by increasing pre-gastric absorption. The TLM-FDTs were developed using a Box-Behnken experimental design with varied doses of crospovidone (CP), croscarmellose sodium (CCS) as super-disintegrants, and camphor as a sublimating agent. In addition, the current study used response surface approach to explore the influence of various formulation and process factors on tablet qualities in order to verify an optimized TLM-FDTs formulation. The optimized TLM-FDTs formula was subsequently evaluated for its in vivo anti-inflammatory activity. TLM-FDTs have good friability, disintegration time, drug release, and wetting time, as well as fast disintegration and dissolution behavior. Significant increase in drug bioavailability and reliable anti-inflammatory efficacy were also observed, as evidenced by considerable reductions in paw thickness in rats following carrageenan-induced rat paw edema. For optimizing and analyzing the effect of super-disintegrants and sublimating agents in the TLM-FDTs formula, the three-factor, three-level full factorial design is a suitable tool. TLM-FDTs are a possible drug delivery system for enhancing TLM bioavailability and could be used to treat rheumatoid arthritis.

【 授权许可】

Unknown