Shelke Santosh, Shahi Sadhana, Jadhav Kiran, Dhamecha Dinesh, Tiwari Roshan, Patil Hemlata
Department of Pharmaceutics, Yash Institute of Pharmacy, Bajaj Nagar, Aurangabad, Maharashtra, 431134, India.
Department of Pharmaceutics, Government College of Pharmacy, Osmanpura, Aurangabad, Maharashtra, 431005, India.
J Mater Sci Mater Med. 2016 Jun;27(6):103. doi: 10.1007/s10856-016-5713-6. Epub 2016 Apr 18.
The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3(2) factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55-381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm(2) and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10(-5) cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability.
本研究的目的是制备并表征用于经鼻途径脑靶向给药的氢溴酸依来曲普坦热可逆凝胶。采用乙醇注入法，通过3（2）析因设计制备乙醇脂质体，其中有两个自变量（大豆卵磷脂浓度和乙醇）和两个响应变量[包封率和囊泡大小（nm）]。对制备的乙醇脂质体进行初步显微镜检查，随后评估药物包封率、囊泡大小分析、zeta电位、多分散性指数和透射电子显微镜（TEM）。TEM证实乙醇脂质体呈球形形态，而马尔文zeta粒度仪证实囊泡大小在191±6.55 - 381.3±61.0 nm范围内。分别使用泊洛沙姆407和卡波姆934作为热可逆聚合物和粘膜粘附聚合物，将乙醇脂质体包封于凝胶中。对乙醇脂质体凝胶进行pH值、粘度、粘膜粘附强度、体外药物释放和通过绵羊鼻黏膜的离体药物渗透评估。发现粘膜粘附强度和pH值分别为4400±45至5500±78.10达因/平方厘米和6.0±0.3至6.2±0.1。优化的乙醇脂质体凝胶制剂（G4）的体外药物释放几乎为100%，24小时后离体渗透量为4980μg/ml，渗透系数为11.94±0.04×10⁻⁵cm/s。鼻黏膜的组织病理学研究证实乙醇脂质体凝胶无毒性。制备的载氢溴酸依来曲普坦乙醇脂质体热可逆凝胶可作为经鼻途径脑靶向给药的更好选择，进而可提高其生物利用度。
