| Hemangioma is a common benign vascular tumors, hemangiomas morbidity as high as 10 to 12% in neonatal. Hemangiomas grow rapidly after birth and slowly faded, but in an important anatomical part or large hemangiomas can cause serious complications and appearance of deformities in infants would cause physical and psychological harm. Propranolol hydrochloride can reduce and softene the hemangioma, and a large number of clinical studies have shown that propranolol hydrochloride promote tumor shrinkage, thinning effect. Lipid cubic crystalline have a bicontinuous aqueous and lipid phase channel region by a certain concentration of the amphipathic substance in the water formed spontaneously. In human skin keratin layer had found with cubic bicontinuous structure similar to the liquid crystal,indicating that the transfer material having a cubic crystal similar biofilms, which may have possible to prepare a transdermal formulation. The purpose of this paper is to prepare a security and stability propranolol hydrochloride liquid crystal transdermal gel, which can improve the bioavailability compared with propranolol hydrochloride tablet. It can provide new clinical treatment for hemangioma.At first, we prepare the different ratios of glyceryl monooleate(GMO) and water liquid gel precursor solution. By examining the visual characteristics, transdermal efficiency, bioadhesive, optical stability, selecting the best glyceryl monooleate-water ratio of 5: 3. On this basis, we ues BOX-Behnken design-response surface methodology to examine the different content of oleic acid, Azone, propylene glycol,and choose the best content which can provide the biggest propranolol hydrochloride liquid permeation performance. we use the Design-Expert7.1 softwore to predict optimal transdermal permeation accelerator content. The results showed that the best content is azone(0.68%) and oleic acid(2.95%). Using this content to prepare a liquid crystal gel, the amount of cumulative through propranolol hydrochloride is446.58μg/cm2,the theoretical and the actual value of the deviation of 2.7%. Use this content as the optimal formulation, and small quantities of amplification, study sample characteristics appearance in bright light and high temperature conditions change, changes in optical stability, content in order to examine its initial stability.The results showed that the samples of the indicators at 25 ℃ or light conditions did not change significantly, under 40 ℃ condition, place 10 days was found to darken,and the drug content decreased slightly, indicating that propranolol hydrochloride liquid gel room temperature stable, storage temperature should be avoided. We use SD rats as experimental animals, investigated the preliminary safey of the propranolol hydrochloride iiquid crystalline gel. The results showed that after using the gel, there were no abnormal activity in rats, and the irritation index was 0, indicate that propranolol hydrochloride liquid gel is safety. At last, we use propranolol hydrochloride tablets for oral administration as a control, 5mg / kg administered,investigated the relative bioavailability of propranolol hydrochloride liquid crystal gel for transdermal delivery. The results show that the relative bioavailability of propranolol hydrochloride using liquid crystal gel transdermal delivery than oral propranolol hydrochloride tablets increased 43.3%, lower peak plasma concentration,time to peak was delayed five hours, extend the average residence time of about 5hours. Thus the formulation is more suitable for treatment of hemangioma, it can provide more safe and effective clinical applications, reducing the frequency of administration, improved patient compliance. |
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