RESUMO
In this paper, a new type of preparation for treatment of initial dry eye disease, thermosensitive in situ gel, was prepared using levocarnitine as a model drug. Poloxamer 407 and poloxamer 188 were used as the gel matrix, and sodium hyaluronate and sodium carboxymethylcellulose were used as bioadhesive materials. Gelation temperature was determined by a rotor method and the prescription was optimized by central composite design-response surface methodology. The pH value, viscosity value and gelation temperature of the optimal prescription were measured. The release of the drug in vitro was examined by dialysis membrane permeation, and retention time of the thermosensitive in situ gel preparation on the rabbit's ocular surface was observed by a slit lamp microscope. The results showed that the dosage of the poloxamer 407 and poloxamer 188 were 20.81% and 3.46%, respectively, and sodium hyaluronate was 0.02%, sodium carboxymethyl cellulose was 0.10% of the optimal formulation of levocarnitine thermosensitive in situ gel. The pH value was 6.90 ± 0.06 at room temperature and the viscosity value started to rise sharply at 27 ℃ of the optimal formulation. The gelation temperature of the optimal preparation before and after dilution by simulated tear fluid were (26.37 ± 0.06) ℃ and (33.57 ± 0.21) ℃, respectively. In the first 240 min, in vitro release rate per unit area of levocarnitine thermosensitive in situ gel was lower than that of solution (P<0.05), and after 600 min, the cumulative release rate of levocarnitine thermosensitive in situ gel could reach more than 80%. The retention time of the thermosensitive in situ gel preparation on rabbit's ocular surface reached about 25 min, at least 5 times as much as that of the solution. The animal experiment was conducted following the National Institutes of Health Guidelines for the use of experimental animals, and approved by the Ethics Committee of the Experimental Animal Center of Beijing University of Chinese Medicine. The levocarnitine thermosensitive in situ gel showed good characteristics and sustained release property and significantly improved the retention time of the drug on the rabbit's ocular surface.
RESUMO
Objective To optimize ambi-extracting and inclusion process of volatile oil from Chuanxiong Rhizoma and Angelicae Sinensis Radix. Methods With yield ratio of volatile oil and ferulic acid content in water extract as evaluation indexes, single factor experiments were used to study the extraction process. With the inclusion rate of volatile oil and yield of inclusion as evaluation indexes, saturated aqueous solution was used to L9(34) orthogonal experiments to reach optimum inclusion process. Results The optimum extraction process of Chuanxiong Rhizoma and Angelicae Sinensis Radix was extracted for 8 hours with 8 folds the amount of water, and without soaking. The validation experiments of extraction of volatile oil and ferulic acid content in water extract were 1.23 mL and 0.387 9 mg/g. The optimum conditions of inclusion process were as follows: volatile oil (mL): β-CD (g) was 1:8;inclusion temperature was 40 ℃; inclusion time was 3 hours. The validation experiments of inclusion rate of volatile oil and yield of inclusion were 74.89% and 72.81%. Conclusion Optimum ambi-extracting and inclusion process of volatile oil from Chuanxiong Rhizoma and Angelicae Sinensis Radix are feasible and stable, witch can provide certain supporting data for preparation production.