title: Cyclodextrin-based telmisartan ophthalmic suspension: Formulation development for water-insoluble drugs.
abstract: In this study, cyclodextrin-based aqueous eye drop suspension of the water insoluble drug telmisartan was developed. Formation of a drug/γ-cyclodextrin complex was enabled by preventing formation of a poorly water-soluble zwitterion using a volatile base that was removed upon drying of the complex powder. Hydroxypropyl methylcellulose was shown to have the overall best effect, stabilizing the complexes without hampering the drug release from the formulation. Two strategies for preparing cyclodextrin-based aqueous eye drop suspensions of telmisartan were investigated, one where hydroxypropyl methylcellulose was added to the medium during preparation of the drug/γ-cyclodextrin complex powder (ternary complex) and the other where hydroxypropyl methylcellulose was added to the complex powder after preparation of the complex (binary complex). The complexation was characterized by DSC, FT-IR and (1)H NMR and the eye drop suspensions formed were examined regarding their stability and in vitro mucoadhesion property. The ternary complex exhibited inferior mucoadhesive property compared to the binary complex. However, the ternary complex was more stable as no notable change in particle size and particle size distribution was observed during storage at 4°C over 6 months (p<0.05) with the mean particle size determined between 2.0 and 2.5μm.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland; Faculty of Pharmacy, Siam University, 38 Petkasem Road, Phasicharoen, Bangkae, Bangkok 10160, Thailand.
authors.forename: Chutimon
authors.initials: C
authors.lastname: Muankaew
authors.affiliation: Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Road, Pathumwan, Bangkok, 10330, Thailand.
authors.forename: Phatsawee
authors.initials: P
authors.lastname: Jansook
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
authors.forename: Hákon Hrafn
authors.initials: HH
authors.lastname: Sigurđsson
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland. Electronic address: thorstlo@hi.is.
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001562:Benzimidazoles / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D001565:Benzoates / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D065546:Drug Liberation; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D006461:Hemolysis / Q000187:drug effects; D065347:Hypromellose Derivatives / Q000737:chemistry; D009883:Ophthalmic Solutions / Q000009:adverse effects / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D012756:Sheep; D012995:Solubility; D013535:Suspensions; D000077333:Telmisartan; D014867:Water / Q000737:chemistry*; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D009883:Ophthalmic Solutions; D013535:Suspensions; D047408:gamma-Cyclodextrins; D014867:Water; D065347:Hypromellose Derivatives; C023792:gamma-cyclodextrin; D000077333:Telmisartan
keywords: Lyophilization; Microparticles; Ophthalmic suspension; Stabilize; Telmisartan; γ-cyclodextrin