Digenis G A, Nosek D, Mohammadi F, Darwazeh N B, Anwar H S, Zavos P M
Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
Pharm Dev Technol. 1999 Aug;4(3):421-30. doi: 10.1081/pdt-100101378.
The purpose of this study was to formulate Nonoxynol-9 (N-9) into a solid coprecipitate form which can be used in preparing pharmaceutically attractive and nonirritating vaginal controlled-release delivery systems (DDSs) such as gelatin capsules (HGC) and tablets. N-9 was coprecipitated with polyvinylpyrrolidone (PVP) with or without iodine to produce solid powders which were incorporated into either (a) bilayer tablet DDSs which possess a fast- (outer) and slow- (inner core) releasing compartment, and (b) HGC DDSs (named Triad HGC) composed of fast- (outer), intermediate- (granules), and slow- (pellets) releasing compartments. The rates of release of iodine and/or [14C]N-9 from the two DDSs were studied in vitro in phosphate buffer at pH 5.0, in human seminal plasma and in vivo after intravaginal administration in rabbits. In all of the above-described release studies, the DDSs were shown to release their N-9 or iodine content rapidly, reaching spermicidal levels within 3 min. This was further substantiated by experiments in which the DDSs were introduced in whole human semen containing live spermatozoa. Complete spermicidal kill was obtained in less than 1 min and in less than 3 min from the bilayer tablet and the Triad HGC, respectively. Furthermore, the release of N-9 from the two DDSs was shown to continue for at least 4 hr in buffers (pH 5.0), human seminal fluid, and after intravaginal administration in rabbits. The resulting powder from the coprecipitation of N-9 and PVP (K-30) can be appropriately formulated into a controlled-released HGC or bilayer tablet to produce vaginal controlled-release DDSs which are nonirritating and have the potential to become effective spermicidal products.
本研究的目的是将壬苯醇醚-9（N-9）制成固体共沉淀物形式，用于制备具有药学吸引力且无刺激性的阴道控释给药系统（DDS），如明胶胶囊（HGC）和片剂。N-9与聚乙烯吡咯烷酮（PVP）在有或没有碘的情况下共沉淀，以产生固体粉末，这些粉末被掺入（a）具有快速（外层）和缓慢（内核）释放隔室的双层片剂DDS中，以及（b）由快速（外层）、中间（颗粒）和缓慢（小丸）释放隔室组成的HGC DDS（称为三联体HGC）。在pH 5.0的磷酸盐缓冲液、人精浆中以及在兔阴道内给药后，体外研究了两种DDS中碘和/或[14C]N-9的释放速率。在上述所有释放研究中，DDS均显示能迅速释放其N-9或碘含量，在3分钟内达到杀精水平。在含有活精子的全人类精液中引入DDS的实验进一步证实了这一点。双层片剂和三联体HGC分别在不到1分钟和不到3分钟内实现了完全杀精。此外，两种DDS中N-9在缓冲液（pH 5.0）、人精液中以及兔阴道内给药后的释放至少持续4小时。N-9与PVP（K-30）共沉淀得到的粉末可适当制成控释HGC或双层片剂，以生产无刺激性且有潜力成为有效杀精产品的阴道控释DDS。
