Factors Involved in Formulation of Oily Delivery System for Proteins Based on PEG-8 Caprylic/Capric Glycerides and Polyglyceryl-6 Dioleate in a Mixture of Oleic Acid with Chitosan Shereen M. Assaf, 1 Nawzat D. Al-Jbour, 2 Ala’a F. Eftaiha, 3 Amani M. Elsayed, 4 Mayyas M. Al-Remawi, 4 Nidal A. Qinna, 5 Babur Chowdhry, 6 Stephen Leharne, 6 and Adnan A. Badwan 2 1 Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan 2 Suwagh Drug Delivery Systems, Subsidiary of the Jordanian Pharmaceutical Manufacturing Co., Naor, Jordan 3 Department of Chemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada 4 Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia 5 Department of Pharmacology, Faculty of Pharmacy, Petra University, Amman, Jordan 6 School of Science, University of Greenwich, Medway Campus, Kent, UK Systematic experimental work is required to improve knowledge related to the use of oily delivery systems. This work aimed to examine the influence of different molecular weights chitosan on for- mation and solubilization ability of w/o system of Labrasol, Plurol Oleique, water and oleic acid. Phase diagrams were constructed. Size measurements were performed for each surfactant in oleic acid. Interfacial tension of chitosan was measured between oleic acid and water at pH 1.5 and 6.25. Effect of chitosan on microemulsion size was studied. When used to deliver rh-insulin to dia- betic rats, the mixture showed reduction in blood glucose compared to control. Keywords Chitosan, insulin, microemulsion, oily system, protein delivery INTRODUCTION Solubilized micellar solutions or so called microemul- sions have gained a wide interest in pharmaceutical formu- lations as possible drug delivery vehicles because of their stability, ease of preparation, low toxicity and ability to solubilize a variety of drugs with improving bioavailability. Such systems are clear, isotropic colloidal mixtures of oil, water, surfactant, and most frequently a cosurfactant. [1–3] Solubilized systems are prepared when a certain amount of a surfactant is able to solubilize both oil and water com- pletely in a single-phase system, under gentle agitation. If the medium is aqueous, oil-in-water (o=w) system is formed, while water-in-oil (w=o) system is formed if the medium is oil. [4,5] The association of surfactants in nonaqueous media is of low cooperativity and results only in smaller and polydis- perse aggregates, with average aggregation number in the range of 1 to 5. [6] However, introduction of even small amounts of water can induce a cooperative self-assembly, leading to the formation of reversed, or inverse, micelles in which the hydrophilic heads of the surfactant molecules comprising the interior region surrounded by an outer region containing the hydrophobic groups and the nonpo- lar solvent. Dipole-dipole interactions hold the hydrophilic heads together in the core. The surfactants used in these sys- tems must necessarily be soluble in the solvent. In these sys- tems there is no sharp change in aggregation number over a narrow concentration range with no marked change in the surface or bulk properties of the solution in that region. Very little information is available on the aggregation numbers of micelles in nonaqueous solvents, and some of it is controversial. [7] In general, the aggregation number in Received 10 November 2009; accepted 22 December 2009. The authors would like to acknowledge the School of Science at Greenwich University for providing the facility for interfacial tension measurements. This work was financially supported by the Jordanian Pharmaceutical Manufacturing Co., Naor, Jordan. Address correspondence to Adnan A. Badwan, Suwagh Drug Delivery, Naor, Jordan. E-mail: jpm@go.com.jo Journal of Dispersion Science and Technology, 32:623–633, 2011 Copyright # Taylor & Francis Group, LLC ISSN: 0193-2691 print=1532-2351 online DOI: 10.1080/01932691003659775 623