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Title: The effect of precipitation techniques on bioadhesive microparticle characteristics
Author: Al-Obaidi, Issraa Rasheed A.
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2011
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A solvent precipitation technique was developed for preparing bioadhesive HPMC microparticles for nasal delivery. Aqueous gels of lactose:HPMC (1:1) were used as a model formulation, added to a precipitating solvent, and the effect of processing parameters such as stirring speed (1000-2000 rpm), needle gauge (19g, 21g and 23g), and dropping rate (5 ml/hour and 10 ml /hour) were studied. The optimal particle size required for nasal delivery (less than 100 (So(Bm))) was obtained using a stirring speed of 8000 rpm, a temperature of 4°C, a dropping rate of 10 ml/ hour, using a 23g needle. Verapamil hydrochloride (VH) and metformin hydrochloride (MH) were investigated as model drugs using the optimised processes. The resultant VH:HPMC (1:1) microparticles achieved a maximum drug loading of only 8.7%, and precipitation of MH:HPMC microparticles in IPA achieved a similar loading. However, MH:HPMC microparticles with a drug loading of 45-53% were obtained with precipitation in acetone. Th is correlated with the relative solubilities of MH in IPA and acetone. In-vitro assessment of adhesion properties of the microparticles showed that the process of precipitation greatly increased the adhesiveness in comparison with HPMC powder alone, due to the formation of a continuous HPMC matrix. MH:HPMC (1:1) microparticles precipitated in acetone provided the optimal combination of adhesive properties and sustained release of drug, and the reasons for this were further investigated using microparticles precipitated from HPMC alone. Bioadhesive performance was found to be dependent on the dehydrated state of the polymer following precipitation, with the most dehydrated formulations showing greater adhesive performance. Dehydration of the aqueous gel was found to be most efficient when the gel was added dropwise to highly agitated acetone. The optimal MH:HPMC (1:1) microparticle formulation was found to be stable following storage under stressed conditions, as a result of dehydration during the precipitation technique.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available