Ali Hatim, Opere Catherine, Singh Somnath
Teva Pharmaceuticals, 223 Quaker Rd, Pomona, New York, 10970, USA.
AAPS PharmSciTech. 2014 Aug;15(4):910-9. doi: 10.1208/s12249-014-0117-8. Epub 2014 Apr 24.
Hydrogen sulfide (H2S) is having many potential pharmacological and physiological actions which reported that therapeutically useful concentration is low (100-160 μM) and a higher concentration could be toxic. Most of its donors produce it on coming into contact with water. All of these problems could be solved by a controlled-release delivery system which does not utilize water in any of its development steps. Therefore, 12 sustained release formulations were prepared by dissolving sodium hydrogen sulfide (NaHS)-a model H2S donor-in polymer solutions, prepared by dissolving polymers (consisted of either polylactide (PLA) or polylactide co-glycolide (PLGA), containing free carboxylic acid or capped allyl ester end group) in a mixture of benzyl benzoate (BB) and benzyl alcohol (BA). The formulation was injected in simulated tear fluid (STF) from which samples were withdrawn at specified times and assayed for NaHS content. We found decrease in burst and overall release with increase in polymer concentration from 10 to 20% w/v. The formulations containing free end group showed significant (p < 0.05) reduction of burst release (11% vs 21%). However, the overall release or the average amount released per hour was found to be significantly (p < 0.05) increased for formulations containing polymers with free end group than those with capped end group. A sustained level of H2S was found to be maintained for 72 h which should be further increased to a month to make it a viable H2S donor delivery system in addition to investigating toxicity profile specifically for the purpose of subconjunctival ocular delivery.
硫化氢(H₂S)具有许多潜在的药理和生理作用,据报道,其治疗有效浓度较低(100 - 160 μM),较高浓度可能有毒。其大多数供体与水接触时会产生硫化氢。所有这些问题都可以通过控释给药系统来解决,该系统在其任何开发步骤中都不使用水。因此,通过将硫化氢供体模型硫氢化钠(NaHS)溶解在聚合物溶液中来制备12种缓释制剂,聚合物溶液是通过将聚合物(由聚乳酸(PLA)或聚乳酸 - 乙醇酸共聚物(PLGA)组成,含有游离羧酸或封端的烯丙基酯端基)溶解在苯甲酸苄酯(BB)和苯甲醇(BA)的混合物中制备的。将制剂注射到模拟泪液(STF)中,在指定时间从中取出样品并测定NaHS含量。我们发现,随着聚合物浓度从10% w/v增加到20% w/v,突释和总体释放减少。含有游离端基的制剂显示突释显著降低(p < 0.05)(11%对21%)。然而,发现含有游离端基聚合物的制剂的总体释放或每小时平均释放量比含有封端端基聚合物的制剂显著增加(p < 0.05)。发现H₂S能持续维持72小时,除了专门针对结膜下眼部给药目的研究毒性特征外,应进一步将其延长至一个月,以使其成为可行的H₂S供体给药系统。