Synthesis, physicochemical properties and ocular pharmacokinetics of thermosensitive <i>in situ</i> hydrogels for ganciclovir in cytomegalovirus retinitis treatment

<p>Ganciclovir (GCV) is one of the most widely used antiviral drugs for the treatment of cytomegalovirus (CMV) retinitis. In this context, the aim of this study was to design <i>in situ</i> thermosensitive hydrogels for GCV ocular delivery by intravitreal injection to achieve sustained drug release behavior and improved ocular bioavailability in the treatment of CMV retinitis. A thermosensitive poly-(β-butyrolactone-co-lactic acid)-polyethylene glycol-poly (β-butyrolactone-co-lactic acid) (PBLA-PEG-PBLA) triblock copolymer was synthesized by ring-opening polymerization and characterization. The GCV-loaded PBLA-PEG-PBLA <i>in situ</i> hydrogels (15%, <i>w/w</i>) were then prepared with drug concentration at 2 mg·mL⁻¹ and the gelation temperatures, rheological properties, <i>in vitro</i> degradation and syringeability of <i>in situ</i> hydrogels for intravitreal injection were also investigated. Membraneless dissolution model was used to explore drug release behavior of PBLA-PEG-PBLA <i>in situ</i> hydrogel. The results indicated that more than 45 and 85% of GCV can be released within 24 and 96 h, respectively, which was verified by a non-Fickian diffusion mechanism. <i>In vivo</i> ocular pharmacokinetics study showed that area under drug-time curve (AUC) and half-life of PBLA-PEG-PBLA <i>in situ</i> hydrogel was higher (AUC was 61.80 μg·mL⁻¹·h (<i>p</i> < .01) and <i>t</i>_1/2 was 10.29 h in aqueous humor; AUC was 1008.66 μg·mL⁻¹·h (<i>p</i> < .01) and <i>t</i>_1/2 was 13.26 h (<i>p</i> < .01) in vitreous) than GCV injection with extended therapeutic activity. Based on obtained results, it was concluded that the thermosenstive PBLA-PEG-PBLA <i>in situ</i> hydrogel is a promising carrier of GCV for intravitreal injection.</p

Improving the topical ocular pharmacokinetics of lyophilized cyclosporine A-loaded micelles: formulation, <i>in vitro</i> and <i>in vivo</i> studies

<p>Dry eye syndrome (DES) is one of the most common disorders of the eye for which combined treatment includes modification of the ocular environment and pathogenic therapies. Cyclosporine A (CsA), a immunosuppressive agent, has been demonstrated to be effective for the treatment of DES but is limited clinically by its low ocular bioavailability due to poor water solubility. In this paper, methoxy poly (ethylene glycol)-poly (lactide) polymer (mPEG-PLA) micelles were investigated as alternative vehicles for the solubilization and delivery of CsA to the eye. The <i>in vitro</i> stability indicated that CsA-loaded micellar lyophilized powder was stable for at least 3 months and the release profile showed a sustained release manner of CsA from micelles physically. <i>In vivo</i> ocular distribution studies demonstrated that the micellar formulations exhibited a 4.5-fold increase in retention effect at eyes compared with 0.05% CsA emulsion. In addition, the <i>in vivo</i> pharmacokinetics profile showed that the CsA-loaded micelles could enhance the retention time, achieving longer effect toward the DES. These studies proposed an effective micelle formulation as a novel ocular drug delivery system to improve solubility and bioavailability of ophthalmic CsA-controlled delivery.</p

Risk assessment of supply chain for pharmaceutical excipients with AHP-fuzzy comprehensive evaluation

<p>As the essential components in formulations, pharmaceutical excipients directly affect the safety, efficacy, and stability of drugs. Recently, safety incidents of pharmaceutical excipients posing seriously threats to the patients highlight the necessity of controlling the potential risks. Hence, it is indispensable for the industry to establish an effective risk assessment system of supply chain. In this study, an AHP-fuzzy comprehensive evaluation model was developed based on the analytic hierarchy process and fuzzy mathematical theory, which quantitatively assessed the risks of supply chain. Taking polysorbate 80 as the example for model analysis, it was concluded that polysorbate 80 for injection use is a high-risk ingredient in the supply chain compared to that for oral use to achieve safety application in clinic, thus measures should be taken to control and minimize those risks.</p