The purpose of this investigation was to encapsulate carvedilol, a model beta-blocker antihypertensive into nano-spanlastics, followed by incorporation into 1% CMC wafer to afford a mucoadhesive buccal drug delivery system, targeting to sidestep the first-pass metabolism, improving the drug absorption and pharmacological effect, achieving non-invasive buccal delivery for treating hypertension. Carvedilol-loaded nano-spanlastics were rendered by ethanol injection technique, using 23 factorial design. The effect of formulation variables was investigated on nano-spanlastic characteristics. The optimal nano-spanlastic formulation (S2; containing 20% Brij 97) exhibited particle size (239.8 ± 5 nm), entrapment efficiency (98. 16 ± 1.44%), deformability index (8.74 ± 0.42 g), and the flux after 24 h (Jmax) (22.5 ± 0.25 (μg/cm2/h) with enhancement ratio 2.87 as well as excellent stability after storage. Permeation study verified the preeminence of the S2 formula. A confocal laser scanning microscope showed deep penetration of S2 through sheep buccal mucosa formula compared to rhodamine B solution. S2-based wafer showed acceptable characters (pH, swelling, drug content, residence time, and release rate). In vivo studies (pharmacodynamic study and biochemical evaluation) showed considerable improvement in blood pressure, the profile of the lipid, oxidant stress biomarkers, and cardiac markers. Histopathological studies revealed the superiority of S2 wafer in the protection of heart tissues over Carvid®. The results achieved indicate that nano-spanlastic-based wafer offers a promising improving trans-buccal carvedilol delivery system.
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Sallam, N.M., Sanad, R.A.B., Ahmed, M.M. et al. Impact of the mucoadhesive lyophilized wafer loaded with novel carvedilol nano-spanlastics on biochemical markers in the heart of spontaneously hypertensive rat models. Drug Deliv. and Transl. Res. (2020). https://doi.org/10.1007/s13346-020-00814-4
- Span 60
- Elastic vesicles
- Ethanol injection
- Buccal mucosa
- Edge activator