Hydrocortisone nanosuspensions for ophthalmic delivery: A comparative study between microfluidic nanoprecipitation and wet milling

• Published in: Journal of controlled release Vol. 149; no. 2; pp. 175 - 181
• Main Authors: Ali, Hany S.M., York, Peter, Ali, Ahmed M.A., Blagden, Nicholas
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 20-01-2011; Elsevier
• Subjects: Animals; bioavailability; Biological and medical sciences; Biological Availability; Chemical Precipitation; Controlled release; cortisol; cost effectiveness; crystal structure; differential scanning calorimetry; Drug Carriers - chemistry; Drug Compounding - methods; drugs; Eye - metabolism; General pharmacology; Hydrocortisone; Hydrocortisone - administration & dosage; Hydrocortisone - pharmacokinetics; Male; Medical sciences; Microfluidics; Milling; Nanostructures - chemistry; Nanosuspension; Nanotechnology - methods; Ophthalmic delivery; Ophthalmic Solutions; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rabbits; Solutions; Suspensions; temperature; wet milling; Wettability; X-ray diffraction; zeta potential; Nanosuspension; Hydrocortisone; Ophthalmic delivery; Controlled release; Microfluidics; Milling; Corticosteroid; Pharmaceutical technology; Steroid hormone; Controlled release form; Control release polymer; Antiinflammatory agent; Grinding(comminution); Ophthalmic preparation; Adrenal hormone; Dosage form; Comparative study; Nanotechnology
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2010.10.007

Recently, drug nanosuspensions have shown a potential for ophthalmic delivery. In this study, a hydrocortisone (HC) nanosuspension (NS) was developed using microfluidic nanoprecipitation as a recent, simple and cost-effective bottom-up technique of drug nanonization. For comparison, a second HC NS was prepared by top-down wet milling procedures. The produced nanosuspensions were characterized for particle size, shape and zeta potential. HC nanosuspensions of approximately 300
nm particle size were produced by adjusting experimental conditions of the two processing techniques. Results of X-ray diffraction and differential scanning calorimetry revealed that HC maintained the crystalline structure upon milling, while predominant amorphous particles were generated after precipitation. Ocular bioavailability of HC nanosuspensions was assessed in albino rabbits using HC solution as a control. A sustained drug action was maintained up to 9
h for the nanosuspensions compared to 5
h for the drug solution. The precipitated and milled NS achieved comparable AUC
0–9h values of 28.06
±
4.08 and 30.95
±
2.2, respectively, that were significantly (
P
<
0.05) higher than that of HC solution (15.86
±
2.7). After 2
months storage at room temperature, the milled HC NS showed good stability with no discernable changes in particle size, whereas the particle size of the precipitated HC NS increased to 440
nm.
Changes in intraocular pressure (IOP) of Albino rabbits after administration of Hc solution and nanosuspensions produced by milling and precipitation.
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