期刊
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
卷 46, 期 9, 页码 1402-1415出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/03639045.2020.1791163
关键词
Lamotrigine; artificial neural networks; Box-behken design; preformulation; thermosetting; hydrogel
资金
- South African Agency for Science and Technology Advancement
The aim of this research was to develop lamotrigine containing thermosetting hydrogel for intranasal administration to manage and treat generalized epilepsy. Thermosetting hydrogels were prepared using different ratios of poloxamer 407 (L127), poloxamer 188 (L68) and Carbopol(R)974 P NF (C974) using the cold production process. Thein situthermosetting hydrogel was optimized using Box Behken design. Co-solvency approach was used to increase the solubility of lamotrigine by dissolving it in propylene glycol and polyethylene glycol 400 (0.2: 0.8) and the resultant solution was incorporated in the hydrogel to manufacture an LTG hydrogel. The presence of a higher amount of L127 resulted in higher viscosity at 22 degrees C and 34 degrees C and decreased the overall release of LTG. An increase in the amount of C974 resulted in a decrease in the pH of the hydrogel. The results show that formulations F10, F12, F13, F14, F15, F16 and F17 exhibited acceptable thermosetting behavior, pH and released adequate Lamotrigine above the minimum effective concentration to treat generalized epilepsy. The optimized formulation exhibited acceptable thermosetting behavior, pH and lamotrigine release but formed a stiff gel at 22 degrees C. The average LTG content of the optimized hydrogel was 5.00 +/- 0.0225 mg/ml with % recovery of 99.17%. The amount of LTG released at 12 h from the optimized hydrogel was 3.21 +/- 0.0155 mg and will be therapeutically effective in the brain after absorptionviathe olfactory region in the nasal cavity.
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