Abstract
First-pass metabolism affects many oral medications and limits the attainment of their therapeutic level. It can be bypassed by administrating buccal dosage forms that allow systemic drug absorption via buccal mucosa. Drugs formulated as buccal medicaments should have an acceptable solubility in saliva. Numerous technologies had been experimented to increase the aqueous solubility of poorly water-soluble drugs e.g. solid dispersion technique. This technique is efficient for improving the solubility and dissolution rate of hydrophobic drugs and consequently improving their bioavailability. Domperidone is an antiemetic drug that undergoes extensive first-pass metabolism, having poor solubility in saliva and poor bioavailability. This study aimed to improve the aqueous solubility of domperidone at pH simulating saliva by preparing multicomponent solid dispersions using different carriers by solvent evaporation method. In vitro dissolution studies showed enhanced dissolution rates of all prepared systems with release kinetics approaching Higuchi model. Ternary solid dispersion (SD) of 1:9:0.25 drug/polyvinylpyrrolidone K30/pluronic F-127, respectively, achieved the highest dissolution rate. Physicochemical characterization of this SD using differential scanning calorimetry, Fourier-transform infrared spectroscopy, powder X-ray diffraction and scanning electron microscopy indicated the presence of an interaction between domperidone and polyvinylpyrrolidone K30 with evidence of drug amorphization that might be responsible for the enhanced dissolution rate. Key words: Domperidone, polyvinylpyrrolidone K30, pluronic F-127, solvent evaporation method, multicomponent solid dispersions, physiochemical characterization.
Highlights
First-pass metabolism is the most popular disadvantage of the orally administrated drugs where this pathway affects drug bioavailability (Waite and Keenan, 2010)
The increment of drug solubility can be explained by solubilization effect of carriers, their improving influence on drug wettability and through the formation of soluble complexes between hydrophobic drug and hydrophilic carrier (Bhole and Patil, 2009; Shah et al, 2012)
This study demonstrated the possibility of improving DMP solubility and dissolution performance by the formulation of solid dispersions
Summary
First-pass metabolism is the most popular disadvantage of the orally administrated drugs where this pathway affects drug bioavailability (Waite and Keenan, 2010). Alternative non-enteral routes of administration can overcome this metabolic pathway allowing the systemic drug absorption, thereby increasing its bioavailability and decreasing metabolite production e.g. sublingual, rectal, inhalation, intravenous, intramuscular and transdermal routes (Rose and Golan, 2008). For a drug to be absorbed, it should have an acceptable solubility at the absorption site. Since many drugs discovered by the technological innovation of combinatorial chemistry are poorly water-soluble entities, it is often difficult to adopt them as candidates for pharmaceutical preparations (Ohara et al, 2005). Several techniques were developed to improve the aqueous solubility of these drugs. The most popular approach is the incorporation of the active hydrophobic component into solid dispersions (Farizon et al, 2013), inclusion complexes (Sreenivasa et al, 2012), inert lipid vehicles (Mirza et al, 2010), surfactant dispersion (Jagdale et al, 2012), self-emulsifying formulations (Zhao et al, 2012), dry emulsions (Ge et al, 2008) and niosomes (Samyuktha and Vedha, 2011)
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