ECTS: 15
Faglige nøgleord: lægemiddelformulering, miceller, fysisk farmaci
Antal Studerende: 1-2
Vejleder: René Holm
Beskrivelse: Parenteral formulations are drug products intended for other administration routes, such as intravenous or subcutaneous injection. The volumes that can be administered intravenously are relatively large, up to about 25 mL for a bolus injection and a Liter when infused. Subcutaneously, however, the injection volume to an adult person is 1,5 to 2,0 mL due to the physiological structures under the skin. Intravenous injections are normally administered by health care professionals due to the relative complex procedure, whereas subcutaneous injection can be given by the patient her/him-self, which could ease the treatment regime for some products. Obtaining a maximal solubility in the formulation vehicle is therefore critical to enable the use of subcutaneous administration, in particular for low water-soluble compounds.
There are five classical formulation approaches for low soluble compounds for parenteral administration when formulating in aqueous vehicles: i) pH adjustments, ii) addition of cosolvents, iii) addition of surfactants, iv) addition of cyclodextrins, and v) formulating with a submicron emulsion. pH adjustment can be used in combination with all the other approaches, however, otherwise combination is in general not beneficial.
pH adjustments cannot be used for neutral compounds and have to be in the range of 5-8 for subcutaneous administration. Cosolvents can influence the tonicity to an extend that is unpleasant for the patient, cyclodextrins may not encapsulate all molecules and emulsions require that the compound can be solubilised in the oil phase, why surfactant in combination with pH is a frequently used strategy. Often surfactant containing formulation are based upon one surfactant and there is general a linear correlation between the surfactant concentration and the solubilisation observed, as demonstrated in a classical study by He and coworkers (2005), however, to the best of my knowledge no one have systematically looked into the combination of different surfactants to characterise if synergistic solubilisation effects could be obtained.
The purpose of this project is therefore to investigate the solubility of a range of different drug compounds in different micellar systems containing mixtures of surfactants to explore if better solubility can be obtained by combination of surfactants, e.g. also by combining with charged surfactants such as SLS and DOSS.
Metoder: Solubility studies, XRPD and HPLC
Referencer:
He Y, Tabibi SE, Yalkowsky SH. Solubilization of two structurally related anticancer drugs: XK-469 and PPA. J Pharm Sci. 2006 Jan;95(1):97-107.
Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov 2004;3:1023–1035.