title: Micromechanical and physical stability analysis of an irradiated poly (lactic-co-glycolic acid) donut-shaped minitablet device for intraocular implantation.
abstract: This study pragmatically characterized the micromechanical and physical stability of a poly(lactic-co-glycolic acid) (PLGA)-based ganciclovir (GCV)-loaded donut-shaped minitablet (DSMT) device for intraocular implantation. Thermal and spectroscopic analysis was performed on various drug-polymer permutations. Porositometric profiles were quantitatively analyzed coupled with qualitatively SEM imaging. The tensile strength (TS) and fracture energy (FE) of the device was also determined pre- and post-γ-sterilization. Inimitably, chemometric and molecular modeling provided a supportive confirmatory tool for establishing fundamental correlative suppositions between the transitioned surface morphology and the micromechanical stability after γ-irradiation. Isotherm plot volumes ranged between -0.028 ± 0.022 and 0.110 ± 0.005 m(2)/g for pre- and post-sterilized devices, respectively, revealing a microporous alteration in porosity. Pre-sterilized devices had larger pores (BJHa=286.22 vs. 192.49 Å) and lower FE (151.301 ± 6.089 N/m) and TS (26.396 ± 1.062 N) values while sterilized devices had crystalline matrices that facilitated the superiorly controlled drug release kinetcs obtained. DSC thermograms displayed the characteristic disordered crystallization of GCV and hydration exotherms resulting from ionization during γ-irradiation. FTIR spectrograms showed fingerprint molecular imprints of GCV and axial stretching of hybridized carbons of PLGA with no subversive drug-polymer interactions after γ-irradiation. Integration of the results inveterately revealed that compression and subsequent γ-irradiation of the device affected desirable micromechanical and solid-state stability behavior.
authors.affiliation: University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology , 7 York Road, Parktown, 2193, Johannesburg, South Africa.
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Michael P
authors.initials: MP
authors.lastname: Danckwerts
authors.forename: Trevor R
authors.initials: TR
authors.lastname: Carmichael
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Riaz A
authors.initials: RA
authors.lastname: Khan
mesh_terms: D003460:Crystallization / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D015774:Ganciclovir / Q000737:chemistry*; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D019654:Lens Implantation, Intraocular; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D013242:Sterilization / Q000379:methods; D013607:Tablets / Q000737:chemistry*; D013718:Tensile Strength
chemical_list: D003692:Delayed-Action Preparations; D011108:Polymers; D013607:Tablets; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015774:Ganciclovir