In vitro-controlled release delivery system for hydrogen sulfide donor.
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 The formulation was injected in simulated tear fluid (STF) from which samples were withdrawn at specified times and assayed for NaHS content.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.
Teva Pharmaceuticals, 223 Quaker Rd, Pomona, New York, 10970, USA.
Hatim
H
Ali
Catherine
C
Opere
Somnath
S
Singh
D001565:Benzoates / Q000737:chemistry; D019905:Benzyl Alcohol / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D006862:Hydrogen Sulfide / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013440:Sulfides / Q000737:chemistry
D001565:Benzoates; D003692:Delayed-Action Preparations; D011091:Polyesters; D011108:Polymers; D013440:Sulfides; D011100:Polyglycolic Acid; C033616:poly(lactide); D019905:Benzyl Alcohol; C006723:benzyl benzoate; C033479:sodium sulfide; D006862:Hydrogen Sulfide