Departamento de Farmacia, UNITEFA, CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina.
Carbohydr Polym. 2013 Oct 15;98(1):380-90. doi: 10.1016/j.carbpol.2013.06.012. Epub 2013 Jun 20.
The effects of binary and ternary systems of acetazolamide (ACZ) with hydroxypropyl-β-cyclodextrin (HP-β-CD) alone or with triethanolamine (TEA) on the crystalline properties, dissolution and intraocular pressure (IOP)-lowering effect were investigated. It was found that the crystal structure of ACZ powder could be modified by the processing conditions. Freeze-drying ACZ powder affected not only the particle morphology but also its polymorphic form and the starting ACZ was converted to pure form A upon freeze-drying treatment. Results provided by DSC/TGA, XRPD, SEM and FT-IR suggested the formation of inclusion complexes between ACZ with HP-β-CD alone or with TEA, obtained by the freeze-drying method and the conversion of the drug into the amorphous state. Binary and ternary systems of ACZ obtained by freeze-drying exhibited significantly enhanced ACZ dissolution rates. The IOP-lowering effects of ACZ and its complexes with HP-β-CD alone or with TEA were studied in normotensive rabbits. Whereas the maximum IOP-lowering effect (~4 mmHg, ~33%), obtained with these binary and ternary lyophilized ACZ systems occurred at around 90 min, the ternary system exhibited a longer maximum IOP-lowering effect peak compared with that of the binary system. These results are in line with those obtained from the dissolution studies, where the ternary system exhibited longer dissolution times compared to the lyophilized binary one. Results obtained from the dissolution studies, also showed that freeze-drying the native crystalline form of ACZ significantly increased the dissolution rate of ACZ, thus improving the IOP-lowering effect of this drug.
研究了乙酰唑胺（ACZ）与羟丙基-β-环糊精（HP-β-CD）的二元和三元体系以及与三乙醇胺（TEA）的二元和三元体系对晶体性质、溶解和眼压（IOP）降低作用的影响。结果发现，ACZ 粉末的晶体结构可以通过加工条件进行修饰。冻干 ACZ 粉末不仅影响颗粒形态，还影响其多晶型形式，起始 ACZ 在冻干处理后转化为纯 A 型。DSC/TGA、XRPD、SEM 和 FT-IR 的结果表明，ACZ 与 HP-β-CD 单独或与 TEA 形成包合复合物，通过冻干法获得，并将药物转化为无定形态。冻干得到的 ACZ 二元和三元体系表现出明显增强的 ACZ 溶解速率。在正常眼压兔中研究了 ACZ 及其与 HP-β-CD 单独或与 TEA 形成的复合物的降眼压作用。虽然这些冻干的二元和三元 ACZ 系统的最大眼压降低作用（4mmHg，33%）发生在大约 90 分钟左右，但与二元系统相比，三元系统表现出更长的最大眼压降低作用峰。这些结果与溶解研究的结果一致，其中三元系统的溶解时间比冻干的二元系统长。溶解研究的结果还表明，冻干 ACZ 的天然晶体形式显著提高了 ACZ 的溶解速率，从而提高了该药物的降眼压作用。
