Pharmacodynamic, pharmacokinetic and physical characterization of cilnidipine loaded solid lipid nanoparticles for oral delivery optimized using the principles of design of experiments.

Cilnidipine (CND), an anti-hypertensive drug, is known to have low oral bioavailability due to its poor aqueous solubility, low dissolution rate and high gut wall metabolism. In the present study, CND loaded compritol based nanoparticles (CND-CMP-NPs) were prepared by emulsification-solvent evaporation method applying the concepts of design of experiments. Critical factors affecting particle size and loading efficiency (LE%) were assessed by hybrid design approach, comprising of Mini Run Resolution IV design followed by Box-Behnken design. Particle size, PDI, zeta potential and LE% of optimized formulations of CND-CMP-NPs were 207.1 ± 2.9 nm, 0.27 ± 0.1, -22.2 ± 1.9 mV and 15.9 ± 1.3% respectively. No significant changes were observed in physical stability of NPs when stored at 25 °C/60% RH over a period of three months. Pharmacokinetic studies revealed that Fabs of CND-CMP-NPs (0.66) was significantly higher than the free CND (0.27). The Cmax and AUC0-∞ of CND-CMP-NPs (572.4 ± 25.3 ng/mL and 5588.6 ± 229.5 ng/mL × h) were significantly higher (Pcal < 0.0001) as compared to free CND (363.6 ± 23.5 ng/mL and 2316.1 ± 163.6 ng/mL × h). MRT of CND-CMP-NPs (9.8 ± 0.9 h) was significantly higher (Pcal < 0.0001) as compared to free CND (5.7 ± 0.5 h). Pharmacodynamic studies showed a maximum of 38% decrease in systolic blood pressure with more than 20% drop in systolic blood pressure sustained for a total duration of 64 h in the case of CND-CMP-NPs as compared to free CND. CND-CMP-NPs not only provide higher and sustained plasma levels of CND but also higher and sustained antihypertensive therapy as compared to free CND.

Anterior chamber migration of a sustained-release dexamethasone intravitreal implant: A case report and review of literature.

The purpose of the study was to report a case of migration of a dexamethasone intravitreal implant (Ozurdex®) into anterior chamber and review the literature pertaining to the anterior chamber migration of implant. Clinical data were collected from a patient, in whom a dexamethasone intravitreal implant migrated to anterior chamber. A review of literature was conducted to analyze additional reports. A 59-year-old aphakic patient with recalcitrant cystoid macular edema due to chronic idiopathic uveitis was treated with intravitreal injection of dexamethasone implant. Migration of the implant into anterior chamber was noted after a month of injection. Since his cornea was clear and intraocular pressure was normal, he was managed conservatively. Sixteen such reports of migration of implant into anterior chamber was analyzed to look into the possible etiologies and outcome. Disruption of lens capsule, large basal iridectomy, and prior vitrectomy are the primary risk factors for migration of dexamethasone implant into the anterior chamber.