Category: Formulation and Quality
Purpose: Taste is one of the most important parameters governing patient compliance. Undesirable taste is one of several important formulation problems that are encountered with certain drug. In this study, guaifenesin (GFN) particles were prepared by two separate coating, each of which formed the drug layer, the coating layer. Fluidized bed was used to coat the two layers. Hypromellose phthalate was evaluated for the taste-masking effect on a model bitter-tasting drug, GFN. The influence of hypromellose phthalate loading (5 - 25% w/w) and GFN particles release profiles was evaluated.
Methods: The particles were prepared in a fluidized bed processor (GPCG-1, Glatt GmbH, Germany). Sugar spheres of 25 – 30 mesh (600 - 710㎛) were coated to two different layering; drug layer and hypromellose phthalate layer. Initial drug-loaded particles with theoretical drug loading of 48% w/w were coated in a fluidized bed processor (GPCG-1, Glatt GmbH, Germany) equipped with a Wurster column (bottom spray assessment). Hypromellose (AnyCoat-C AW4) solution was used as drug layering binders at 5% w/w solids by adding ethanol and distilled water (8:2 ratio) and diacetylated monoglyceride was used as plasticizer. Drug layering conditions within the fluidized bed equipment were as follows; inlet air temperature 70℃; product temperature 52℃; fluidization air flow 7.5m/s; atomizing air pressure 2bar and a spray rate 15g/min. Approximately 1kg of particles was used for the taste-masking coating. A 10% w/w solution of hypromellose phthalate (AnyCoat-P HP-55) in acetone and ethanol mixed solution (1:1 ratio) was applied by atomization. Diacetylated monoglyceride was used as a plasticizer in the hypromellose phthalate coating. The dispersion was sprayed onto GFN loaded particles with the various hypromellose phthalate-loading weights (5, 10, 15, 20, 25% w/w). The process parameters were mentioned as follow; inlet air temperature 55 - 60℃; product temperature 44 - 47℃; fluidization air flow 7m/s; atomizing air pressure 2bar and a spray rate 20g/min. In vitro dissolution tests of particles were performed using USP I dissolution apparatus (ERWEKA DT1420I) rotating at 50rpm in 900mL at pH 1.2 and pH 6.8 buffer at 37℃. The drug release was determined spectrophotometrically at 272nm. Morphological characteristics of coated particles were analyzed by scanning electron microscopy (SEM).
Results: Coating of the particles with hypromellose phthalate provided taste protection by delaying dissolution and extending the time for clearing the particles from the mouth. Hypromellose phthalate, a polymer which is insoluble below pH5.5 or in the absence of cations appeared to offer the best potential in terms of both taste protection and bioavailability. Diacetyl monoglyceride was included in the coating solution as a plasticizer. To determine the optimum amount of polymer to apply, a series of coated guaifenesin particles was prepared by application of 5 – 25% hypromellose phthalate. Release rates of guaifenesin from the coated particles using pH 1.2 and pH 6.8 buffers. Drug release was significantly decreased according to coating weight increased at pH 1.2 buffer. No release of guaifenesin was observed at all time ranges with coatings above 25% at pH 1.2.
Without this acid-insoluble coating encapsulating the particles, a substantial percentage of guaifenesin would be released. At pH 6.8 the release was much faster but still dependent on the coating level. Over 90% of guaifenesin was release within 30 mins at pH 6.8 buffer.
SEM images showed that the particles had a satisfactory surface morphology and also two layers, drug layer and hypromellose phthalate layer were well-formed.
Conclusion: Particle coating by using hypromellose phthalate was effective for taste-masking on model bitter-drug, guaifenesin. Also, we evaluated the drug release dependent on coating weight. Release rate was minimized at the most coating weight of 25%.
Juhee Shin– Researcher, LOTTE FINE CHEMICAL, Incheon, Inch'on-jikhalsi, Republic of Korea