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Ocular absorption and irritation of pilocarpine prodrug is modified with buffer, polymer, and cyclodextrin in the eyedrop.
Pharm Res 1995; 12(4):529-33PR

Abstract

The influence of buffer, viscosity and cyclodextrin on the ocular absorption and irritation of a pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpic acid diester, was studied in albino rabbits. The prodrug solutions, equivalent to 0.5% pilocarpine, were prepared in 0, 10, 20, 50, or 75 mM citrate buffer at pH 5.0. Viscosity of the solutions (20, 50 or 115 cP) was modified with hydroxypropyl methylcellulose. 2-hydroxypropyl-beta-cyclodextrin (HPCD) was included at concentrations 5, 10 and 15% (w/v). The formulations were compared to a commercial pilocarpine eyedrop (1.7%). Ocular irritation was graded in a double-masked experiment and miosis was used as a bioassay for pilocarpine delivery to the iris. The prodrug showed decreased peak and prolonged duration of miosis compared to pilocarpine, but it caused ocular irritation. Increasing buffer strength decreased and elevated viscosity intensified the miotic response and irritation by the pilocarpine prodrug. HPCD decreased both the ocular delivery of pilocarpine and the irritation by the prodrug, but the net effect was positive. Thus, administering 1.0% of pilocarpine as a prodrug with 15% (w/v) HPCD, the irritation was at the same level with the commercial pilocarpine eyedrop, but the ocular delivery was substantially improved. In conclusion, the ocular delivery of the pilocarpine prodrug may be enhanced in relation to its local irritation by properly combining buffer, viscosity and HPCD.

Authors+Show Affiliations

Department of Pharmaceutical Technology, University of Kuopio, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7596987

Citation

Suhonen, P, et al. "Ocular Absorption and Irritation of Pilocarpine Prodrug Is Modified With Buffer, Polymer, and Cyclodextrin in the Eyedrop." Pharmaceutical Research, vol. 12, no. 4, 1995, pp. 529-33.
Suhonen P, Järvinen T, Lehmussaari K, et al. Ocular absorption and irritation of pilocarpine prodrug is modified with buffer, polymer, and cyclodextrin in the eyedrop. Pharm Res. 1995;12(4):529-33.
Suhonen, P., Järvinen, T., Lehmussaari, K., Reunamäki, T., & Urtti, A. (1995). Ocular absorption and irritation of pilocarpine prodrug is modified with buffer, polymer, and cyclodextrin in the eyedrop. Pharmaceutical Research, 12(4), pp. 529-33.
Suhonen P, et al. Ocular Absorption and Irritation of Pilocarpine Prodrug Is Modified With Buffer, Polymer, and Cyclodextrin in the Eyedrop. Pharm Res. 1995;12(4):529-33. PubMed PMID: 7596987.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ocular absorption and irritation of pilocarpine prodrug is modified with buffer, polymer, and cyclodextrin in the eyedrop. AU - Suhonen,P, AU - Järvinen,T, AU - Lehmussaari,K, AU - Reunamäki,T, AU - Urtti,A, PY - 1995/4/1/pubmed PY - 1995/4/1/medline PY - 1995/4/1/entrez SP - 529 EP - 33 JF - Pharmaceutical research JO - Pharm. Res. VL - 12 IS - 4 N2 - The influence of buffer, viscosity and cyclodextrin on the ocular absorption and irritation of a pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpic acid diester, was studied in albino rabbits. The prodrug solutions, equivalent to 0.5% pilocarpine, were prepared in 0, 10, 20, 50, or 75 mM citrate buffer at pH 5.0. Viscosity of the solutions (20, 50 or 115 cP) was modified with hydroxypropyl methylcellulose. 2-hydroxypropyl-beta-cyclodextrin (HPCD) was included at concentrations 5, 10 and 15% (w/v). The formulations were compared to a commercial pilocarpine eyedrop (1.7%). Ocular irritation was graded in a double-masked experiment and miosis was used as a bioassay for pilocarpine delivery to the iris. The prodrug showed decreased peak and prolonged duration of miosis compared to pilocarpine, but it caused ocular irritation. Increasing buffer strength decreased and elevated viscosity intensified the miotic response and irritation by the pilocarpine prodrug. HPCD decreased both the ocular delivery of pilocarpine and the irritation by the prodrug, but the net effect was positive. Thus, administering 1.0% of pilocarpine as a prodrug with 15% (w/v) HPCD, the irritation was at the same level with the commercial pilocarpine eyedrop, but the ocular delivery was substantially improved. In conclusion, the ocular delivery of the pilocarpine prodrug may be enhanced in relation to its local irritation by properly combining buffer, viscosity and HPCD. SN - 0724-8741 UR - https://www.unboundmedicine.com/medline/citation/7596987/Ocular_absorption_and_irritation_of_pilocarpine_prodrug_is_modified_with_buffer_polymer_and_cyclodextrin_in_the_eyedrop_ DB - PRIME DP - Unbound Medicine ER -