Positively charged self-emulsifying oil formulation for improving oral bioavailability of progesterone.
Positively charged self-emulsifying oil formulation for improving oral bioavailability of progesterone.
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DOI：
10.3109/10837459609029889
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发表时间：
1996-07-01
影响因子：
3.4
通讯作者：
Benita, S
中科院分区：
文献类型：
--
作者：
Gershanik, T;Benita, S
开发并表征了由吐温80、苯甲醇（BA）、油酸乙酯（EO）和油胺（OA）组成的自乳化油制剂（SEOF），其能够在水溶液或缓冲液稀释时产生带正电荷的亚微乳液。制剂的正电荷归因于阳离子脂质OA在稀释的SEOFs的油/水界面处的定位。二元相图分析表明，在连续水相稀释条件下，SEOF引发了渐进的反相行为。在无限稀释时，仅当制剂中BA浓度不超过50%时才形成细亚微米o/w乳剂。在整个生理范围内的pH值的变化，自乳化过程没有显着的影响。在急性毒性研究中观察到的神经毒性作用归因于BA，因为相同BA剂量的简单水溶液引起相似的不良反应，因此使用SEOF溶剂稀释获得的含3% BA的浓缩乳剂进行急性毒性研究。然而，当给予的剂量是可能给予人类的潜在剂量的30倍时，没有发现任何毒性作用。使用几种不同的孕酮液体剂型在年轻雌性大鼠中进行的比较口服生物利用度研究表明，在所研究的那些剂型中，仅带正电荷的SEOF可以被认为是口服孕酮的潜在有效剂型，因为它引起了最高和最令人满意的吸收曲线。
A self-emulsifying oil formulation (SEOF) comprised of Tween 80, benzyl alcohol (BA), ethyl oleate (EO), and oleylamine (OA), able to produce positively charged submicron emulsions upon aqueous or buffer dilution, was developed and characterized. The positive charge of the formulation was attributed to the localization of the cationic lipid, OA, at the oil/water interface of the diluted SEOFs. Binary phase diagram analysis of the basic lipophilic system showed that the SEOF elicited progressive inverse phase behavior under continuous aqueous phase dilution. At infinite dilution fine submicron o/w emulsions were formed only when BA concentrations did not exceed 50% in the formulation. The self-emulsification process was not markedly affected by the variation in pH over the entire physiological range. The neurotoxic effects observed in acute toxicity studies with the concentrated emulsion containing 3% BA obtained from the dilution of the SEOF vehicle were attributed to the BA since a simple aqueous solution at the same BA dose caused similar adverse effects. However, no toxic effects were noticed when the dose administered was 30 times the potential dose that could probably be administered to humans. Comparative oral bioavailability studies in young female rats using several different liquid dosage forms of progesterone indicated that of those studied, only the positively charged SEOF could be considered a potential effective dosage form for oral administration of progesterone since it elicited the highest and most satisfactory absorption profile.