Ocular pharmacokinetics of acetazolamide from intravitreal implants by high-performance liquid chromatography coupled to tandem mass spectrometry.

Glaucoma, a leading cause of irreversible blindness, affects about 70 million people globally. Its treatment focuses on reducing intraocular pressure. Acetazolamide, a potent anti-glaucoma drug, is currently used only systemically due to low solubility and permeation, which cause severe side effects. Developing topical medications with acetazolamide requires robust analytical methods for its detection in biological samples. In this context, this study aimed to develop a method to quantify acetazolamide in rabbit vitreous humor samples. The method involved a simple, fast, inexpensive, and environmentally friendly protein precipitation step for sample preparation, needing just 50 µL of sample and 200 µL of organic solvent, with adequate recovery. This was combined with high-performance liquid chromatography coupled to tandem mass spectrometry, enabling highly sensitive (LOQ of 5 ng/mL) quantification within only 5 min. The method proved to be selective, precise, and accurate, with well-fitted analytical curves, with no carryover, and no matrix effect impacting reliability. The method was successfully applied to analyze vitreous humor samples from rabbits in pharmacokinetic studies, monitoring drug release from intravitreal implants. Results showed a controlled release profile, with a maximum drug concentration (Cmax) of 426.01 ± 64.57 ng/mL, time to reach Cmax (Tmax) of 28 days, and area under the curve (AUC0-42 and AUC0-∞) of 7722.66 ± 1125.96 ng days/mL and 8998.11 ± 1311.92 ng days/mL, respectively. The device demonstrated significantly slower elimination, ensuring therapeutic levels for an extended period when compared to intravitreal injection.

Development and characterization of PLGA-Bupivacaine and PLGA-S75: R25 Bupivacaine (Novabupi®) biodegradable implants for postoperative pain

Abstract In the hospital environment, postoperative pain is a common occurrence that impairs patient recovery and rehabilitation and lengthens hospitalization time. Racemic bupivacaine hydrochloride (CBV) and Novabupi® (NBV) (S (-) 75% R (+) 25% bupivacaine hydrochloride) are two examples of local anesthetics used in pain management, the latter being an alternative with less deleterious effects. In the present study, biodegradable implants were developed using Poly(L-lactide-co-glycolide) through a hot molding technique, evaluating their physicochemical properties and their in vitro drug release. Different proportions of drugs and polymer were tested, and the proportion of 25%:75% was the most stable for molding the implants. Thermal and spectrometric analyses were performed, and they revealed no unwanted chemical interactions between drugs and polymer. They also confirmed that heating and freeze-drying used for manufacturing did not interfere with stability. The in vitro release results revealed drugs sustained release, reaching 64% for NBV-PLGA and 52% for CBV-PLGA up to 30 days. The drug release mechanism was confirmed by microscopy, which involved pores formation and polymeric erosion, visualized in the first 72 h of the in vitro release test. These findings suggest that the developed implants are interesting alternatives to control postoperative pain efficiently.