The most popular and convenient route of drug administration remains the oral route, however, protein and peptide drugs such as insulin have poor membrane permeability and stability in the gastrointestinal tract. Absorption enhancers can be added to drug delivery systems to overcome the epithelial cell membrane permeability problem. Although previous studies have shown that aloe leaf materials improve the transport of drugs across intestinal epithelia, their performance in solid oral dosage forms has not yet been investigated. Beads containing insulin and each of the selected absorption enhancers (i.e. Aloe ferox, Aloe marlothii and Aloe vera gel materials) were produced by extrusion-spheronisation, using a full factorial design to optimise the formulations based on transepithelial electrical resistance (TEER) reduction of Caco-2 cell monolayers as response. The optimum bead formulations were evaluated in terms of friability, mass variation, particle surface texture, shape, size and dissolution. The transport of insulin across excised pig intestinal tissue from the optimised bead formulations was determined over a 2 h period. The samples obtained from the transport studies were analysed for insulin content by means of high-performance liquid chromatography (HPLC). The results showed that the TEER reduction, as an indication of tight junction modulation, obtained for the bead formulations containing aloe materials was concentration dependent. Furthermore, inclusion of croscarmellose sodium (Ac-di-sol®) as a disintegrant showed an enhanced TEER reduction effect in combination with the aloe gel materials. Dissolution profiles indicated that the beads containing aloe leaf materials in conjunction with insulin, released the insulin within an hour. In accordance with the TEER reduction results, the A. marlothii and A. vera materials containing beads showed similar increased insulin delivery across excised pig intestinal tissue, which was pronouncedly higher than that of the control group (insulin alone). It can be concluded that beads containing aloe leaf materials have high potential as effective delivery systems for protein therapeutics such as insulin via the oral route of administration. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

The most popular and convenient route of drug administration remains the oral route, however, protein and peptide drugs such as insulin have poor membrane permeability and stability in the gastrointestinal tract. Absorption enhancers can be added to drug delivery systems to overcome the epithelial cell membrane permeability problem. Although previous studies have shown that aloe leaf materials improve the transport of drugs across intestinal epithelia, their performance in solid oral dosage forms has not yet been investigated. Beads containing insulin and each of the selected absorption enhancers (i.e. Aloe ferox, Aloe marlothii and Aloe vera gel materials) were produced by extrusion-spheronisation, using a full factorial design to optimise the formulations based on transepithelial electrical resistance (TEER) reduction of Caco-2 cell monolayers as response. The optimum bead formulations were evaluated in terms of friability, mass variation, particle surface texture, shape, size and dissolution. The transport of insulin across excised pig intestinal tissue from the optimised bead formulations was determined over a 2 h period. The samples obtained from the transport studies were analysed for insulin content by means of high-performance liquid chromatography (HPLC). The results showed that the TEER reduction, as an indication of tight junction modulation, obtained for the bead formulations containing aloe materials was concentration dependent. Furthermore, inclusion of croscarmellose sodium (Ac-di-sol®) as a disintegrant showed an enhanced TEER reduction effect in combination with the aloe gel materials. Dissolution profiles indicated that the beads containing aloe leaf materials in conjunction with insulin, released the insulin within an hour. In accordance with the TEER reduction results, the A. marlothii and A. vera materials containing beads showed similar increased insulin delivery across excised pig intestinal tissue, which was pronouncedly higher than that of the control group (insulin alone). It can be concluded that beads containing aloe leaf materials have high potential as effective delivery systems for protein therapeutics such as insulin via the oral route of administration. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

Approximately 350 million people worldwide suffer from diabetes mellitus (DM) and this number increases yearly. Since the discovery and clinical application of insulin in 1921, subcutaneous injections have been the standard treatment for DM. Because insulin is hydrophilic and has a high molecular weight and low bioavailability, this molecule is poorly absorbed if administered orally. The aim of this study is to evaluate nasal delivery systems for insulin, using Sprague Dawley rats as the nasal absorption model. Pheroid technology and N-trimethyl chitosan chloride (TMC) with different dosages of insulin (4, 8 and 12 IU/kg bodyweight insulin) was administered in the left nostril of the rat by using a micropipette. Pheroid technology is a patented (North-West University) carrier system consisting of a unique oil/water emulsion that actively transports drug actives through various physiological barriers. These formulations were administered nasally to rats in a volume of 100 p/kg bodyweight in different types of Pheroids (vesicles, with a size of 1.7 1 - 1.94 pm and microsponges, with a size of 5.7 1 - 8.25 pm). The systemic absorption of insulin was monitored by measuring arterial blood glucose levels over a period of 3 hours. The TMC formulation with 4 IU/kg insulin produced clinically relevant levels of insulin in the blood and as a result also the maximal hypoglycaemic effect. TMC is a quaternary derivative of chitosan and is able to enhance the absorption of various peptide drugs by opening tight junctions between epithelial cells. Pheroid formulations were also effective in lowering blood glucose levels but only at higher doses (8 and 12 IU/kg) of insulin. This study indicated that Pheroid rnicrosponges had a faster onset of action and a slightly better absorption of insulin when compared to Pheroid vesicles, but many more studies are needed in this field. Although the results of this study with absorption enhancers are encouraging, nasal insulin bioavailability is still very low, and the Pheroid formulations and long-term safety of nasal insulin therapy have yet to be investigated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Approximately 350 million people worldwide suffer from diabetes mellitus (DM) and this number increases yearly. Since the discovery and clinical application of insulin in 1921, subcutaneous injections have been the standard treatment for DM. Because insulin is hydrophilic and has a high molecular weight and low bioavailability, this molecule is poorly absorbed if administered orally. The aim of this study is to evaluate nasal delivery systems for insulin, using Sprague Dawley rats as the nasal absorption model. Pheroid technology and N-trimethyl chitosan chloride (TMC) with different dosages of insulin (4, 8 and 12 IU/kg bodyweight insulin) was administered in the left nostril of the rat by using a micropipette. Pheroid technology is a patented (North-West University) carrier system consisting of a unique oil/water emulsion that actively transports drug actives through various physiological barriers. These formulations were administered nasally to rats in a volume of 100 p/kg bodyweight in different types of Pheroids (vesicles, with a size of 1.7 1 - 1.94 pm and microsponges, with a size of 5.7 1 - 8.25 pm). The systemic absorption of insulin was monitored by measuring arterial blood glucose levels over a period of 3 hours. The TMC formulation with 4 IU/kg insulin produced clinically relevant levels of insulin in the blood and as a result also the maximal hypoglycaemic effect. TMC is a quaternary derivative of chitosan and is able to enhance the absorption of various peptide drugs by opening tight junctions between epithelial cells. Pheroid formulations were also effective in lowering blood glucose levels but only at higher doses (8 and 12 IU/kg) of insulin. This study indicated that Pheroid rnicrosponges had a faster onset of action and a slightly better absorption of insulin when compared to Pheroid vesicles, but many more studies are needed in this field. Although the results of this study with absorption enhancers are encouraging, nasal insulin bioavailability is still very low, and the Pheroid formulations and long-term safety of nasal insulin therapy have yet to be investigated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.