Agglomerates Containing Pantoprazole Microparticles: Modulating the Drug Release

Abstract

Abstract. Pantoprazole-loaded microparticles were prepared using a blend of Eudragit® S100 and Methocel® F4M. The accelerated stability was carried out during 6 months at 40°C and 75% relative humidity. In order to improve technological characteristics of the pantoprazole-loaded microparticles, soft agglomerates were prepared viewing an oral delayed release and gastro-resistant solid dosage form. The agglomeration was performed by mixing the pantoprazole microparticles with spray-dried mannitol/ lecithin powders. The effects of factors such as the amount of lecithin in the spray-dried mannitol/lecithin powders and the ratio between pantoprazole microparticles and spray-dried mannitol/lecithin powders were evaluated. The pantoprazole-loaded microparticles present no significant degradation in 6 months. The agglomerates presented spherical shape, with smooth surface and very small quantity of nonagglomerated particles. The agglomerates presented different yields (35.5-79.0%), drug loading (58-101%), and mechanical properties (tensile strength varied from 44 to 69 mN mm −2 ), when the spraydried mannitol/lecithin powders with different lecithin amounts were used. The biopharmaceutical characteristics of pantoprazole microparticles, i.e., their delayed-release properties, were not affected by the agglomeration process. The gastro-resistance of the agglomerates was affected by the amount of spray-dried mannitol/lecithin powders. The ratio of lecithin in the spray-dried mannitol/lecithin powders was the key factor in the agglomerate formation and in the drug release profiles. The agglomerates presenting better mechanical and biopharmaceutical characteristics were prepared with 1:2 (w/w) ratio of pantoprazole-loaded microparticles and mannitol/lecithin (80:20) powder.

Formulation of Dosage Forms with Proton Pump Inhibitors: State of the Art, Challenges and Future Perspectives

“…Their advantages include the ability to improve the stability and bioavailability of the drug substance, modification and control of its release site and rate. The most common methods of microparticle production are the solvent evaporation or emulsification method [ 51 , 52 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 ] and spray-drying [ 199 , 200 , 215 , 216 , 217 , 218 , 219 , 220 ]. The advantage of the latter over the other methods is the ease of process scale-up [ 215 ].…”

“…Among the most commonly used polymers for the manufacturing of microparticles containing proton pump inhibitors are methacrylate derivatives such as Eudragit S and L [ 200 , 202 , 209 , 211 , 215 , 216 , 217 , 219 , 222 ], as well as Eudragit RS/RL [ 199 , 205 , 206 , 214 , 220 ]. Although Eudragit S and L are used to make delayed-release forms of the drug, they can also be used as polymers to formulate sustained-release microparticles [ 200 , 202 , 209 , 211 , 215 , 216 , 217 , 219 , 222 ]. In addition, cellulose derivatives such as ethyl cellulose, HPMC or hydroxypropylmethyl cellulose phthalate are also utilized [ 198 , 203 , 204 , 207 , 208 , 213 , 223 ].…”

Anti-inflammatory flurbiprofen nasal powders for nose-to-brain delivery in Alzheimer’s disease

“…1, F15_70) compared to those without the phospholipid. They were coated by lecithin [45,46] and partially aggregated because lecithin acted as an agglomerating agent. Laser light scattering analysis confirmed that these particles were 4-fold as bigger as without lecithin (Table 2).…”

Dry powdered aerosols of diatrizoic acid nanoparticle agglomerates as a lung contrast agent

“…To address this problem, a controlled nanoparticle agglomeration process has been developed where particles exhibiting an aerodynamic diameter from 1 to 5 µm are created to bypass the mouth and throat, resulting in augmented deposition in the lung periphery (Bailey et al, 2008; El-Gendy et al, 2009; Plumley et al, 2009; Schoubben et al, 2010; Tsapis et al, 2002). These porous agglomerates consist of closely-packed nanoparticles that may be easily disseminated throughout the lung (El-Gendy and Berkland, 2009; Raffin et al, 2009; Shi et al, 2007; Tsapis et al, 2002). …”