Abstract
Objective: This study aims to prepare and optimize indomethacin freeze-dried sublingual tablets (IND-FDST) by utilizing a quality by design (QbD) approach to achieve rapid drug dissolution and simultaneously bypassing the GIT for better patient tolerability. Methods: A screening study was utilized to determine the most significant factors which the quality attributes, namely disintegration time and % friability. Then an optimization study was conducted using a full response surface design to determine the optimized formula by varying the amount of the matrix-forming polymer (gelatin) and super disintegrant (croscarmellose sodium (CCS)). The variables' effect on the % friability, disintegration time, wetting time, and amount of drug release after 10 min (%Q10) was studied. The optimized formula was tested for compatibility, morphology as well as stability studies under accelerated conditions in addition to the in vivo pharmacodynamics in rats. QbD was adopted by utilizing a screening study to identify the significant formulation factors followed by a response surface optimization study to determine the optimized IND-FDST formulation. Results: Optimized IND-FDST comprised of gelatin/CCS combination in a ratio of 1:1 possessed adequate %friability (0.73±0.03%), disintegration time (25.40±1.21 seconds), wetting time (3.49±0.68 seconds), and % Q10 (100.99±5.29%) as well as good stability under accelerated conditions. IND-FDST also showed significant inhibition of edema, tumour necrosis factor-alpha, and interleukin-6 release in vivo compared to the oral market product by 70%, 42%, and 65%, respectively. Conclusion: QbD presents a successful approach in the optimization of a successful IND-FDST formula that showed superior in vivo and in vitro characteristics.
Highlights
Oral drug delivery is the most customarily used route among all other drug administration routes [1] because of its recognizable advantages such as; its ease of application, ameliorate patient compliance, slightest sterility conditions needed, and high flexibility in developing the dosage form [2, 3]
Sodium alginate and gelatin were purchased from AVI-CHEM Laboratories, (Mumbai, India)
The results revealed that the gelatin/CCS combination showed the most desirable attributes and was included in the optimization study
Summary
Oral drug delivery is the most customarily used route among all other drug administration routes [1] because of its recognizable advantages such as; its ease of application, ameliorate patient compliance, slightest sterility conditions needed, and high flexibility in developing the dosage form [2, 3]. The use of the sublingual route offers various advantages, such as ease of preparation and the ability to bypass the GIT harsh conditions [5]. Freeze-dried sublingual tablets have attracted much attention from researchers as it offers tablets of high porosity which allows better exposure of the drug to the saliva in the mouth resulting in immediate disintegration and dissolution of the tablet when placed under the tongue [11,12,13,14,15,16]
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