title: In vitro pharmaceutical characterization and statistical optimization of a novel topically applied instantly-soluble solid eye drop matrix.
abstract: Ocular diseases of the anterior segment of the eye are increasing and the development of novel drug delivery systems for improved treatment is necessary. The aim of this study was therefore to design and evaluate an instantly-soluble solid eye drop (ISED) for topical ophthalmic drug delivery of the model drug timolol maleate. The porous nature of the lyophilized ISED resulted in rapid fluid ingression, immediate hydration, and dissolution of the ocular matrix. The ISED was lyophilized employing hydroxypropylcellulose and pluronic® F68 as the matrix forming polymers. Polyacrylic acid sodium enhanced the solubility of the ISED, di-glycine, an anti-collapsing agent, while maltodextrin improved the matrix resilience. A statistical design was employed for optimizing the texture, disintegration, and the mean dissolution time (MDT50%) of the ISED. Results revealed that a robust rapidly disintegrating ISED was produced with the fastest disintegration time recorded at 0.20 s and drug release between 79 and 96%. In addition, improved corneal drug permeation was observed compared to pure timolol dispersion. The maltodextrin concentration significantly affected the ISED matrix resilience (p = 0.007) and pluronic F68 had a greater impact on disintegration time (p = 0.000) and MDT (p = 0.000). The ISED formulation may be a promising alternative to the use of liquid eye drops for topical ophthalmic drug delivery.
authors.affiliation: a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences , School of Therapeutic Sciences, University of the Witwatersrand , Johannesburg , Parktown, South Africa and.
authors.forename: Raeesa M
authors.initials: RM
authors.lastname: Moosa
authors.affiliation: a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences , School of Therapeutic Sciences, University of the Witwatersrand , Johannesburg , Parktown, South Africa and.
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.affiliation: a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences , School of Therapeutic Sciences, University of the Witwatersrand , Johannesburg , Parktown, South Africa and.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.affiliation: a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences , School of Therapeutic Sciences, University of the Witwatersrand , Johannesburg , Parktown, South Africa and.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences , School of Therapeutic Sciences, University of the Witwatersrand , Johannesburg , Parktown, South Africa and.
authors.forename: Lomas K
authors.initials: LK
authors.lastname: Tomar
authors.affiliation: a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences , School of Therapeutic Sciences, University of the Witwatersrand , Johannesburg , Parktown, South Africa and.
authors.forename: Charu
authors.initials: C
authors.lastname: Tyagi
authors.affiliation: b Department of Neurosciences, Division of Ophthalmology, Faculty of Health Sciences , University of the Witwatersrand , Johannesburg , Parktown, South Africa.
authors.forename: Trevor R
authors.initials: TR
authors.lastname: Carmichael
authors.affiliation: a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, Faculty of Health Sciences , School of Therapeutic Sciences, University of the Witwatersrand , Johannesburg , Parktown, South Africa and.
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
keywords: Corneal permeation; Face-Centred Central Composite Design; lyophilized instantly soluble matrix; maltodextrin; ocular drug delivery; pluronic® F68; timolol maleate