Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed.In a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

Continuous melt granulation to develop high drug loaded sustained release tablet of Metformin HCl

The present work explores the application of melt granulation technology to develop a high drug loaded sustained release matrix tablet of Metformin HCl using hydroxypropylcellulose(HPC) as a hydrophilic binder and stearic acid as an extrusion aid for producing cohesive granules. This novel approach allowed the use of a minimum number of excipients to reduce the tablet size, and to enhance compressibility of the drug. This also offered a cost effective method owing to the elimination of a ‘drying step’ prevalent in wet granulation method.Moreover, this research also focuses on resolving the processability issues associated with the use of HPC Nisso-H at high drug loading. The thermal lubricants were screened for this purpose and evaluated for their impact on extrudability, granule and tablet characteristics. Stearic acid was selected as the thermal lubricant, which not only contributed to the inhibition of burst release, but also improved the flow property of the granules.The developed matrix tablet(75% drug loading) resulted in 670 mg of weight for 500 mg dose strength and showed sustained drug release over 10 h. When compared, with conventional granulation techniques, it was observed that, under identical compression force, the tablet prepared by MG exhibited superior compactibility along with tablet hardness and optimal drug release profile. FTIR suggested nonexistence of chemical interaction between the drug and the other excipients while XRD and DSC analysis revealed the crystalline state of the drug.Furthermore, the results obtained from Raman spectroscopy proved the uniform distribution of the Metformin HCl and polymer in the final dosage form. This technology leads to the manufacture of sustained release matrix formulation with reduced tablet size of a high dose,highly water soluble drug otherwise difficult to process using standard batch-granulation.

Comparison in vitro permeation of curcumin from topical gels by liquid chromatography tandem mass spectrometry

Objective： To fred a more effective method of topical transdermal delivery of curcumin. Methods： We prepared curcumin carbopol （CRB） 974P and hydroxypropylcellulose （HPC） gel formulations containing menthol or Azone as permeation enhancers In this study, negative mode electrospray ionization and a triple quadruple LC/MS/MS instrument operated in multiple reaction mode was used for curcumin detection. The assay was linear over a concentration range of 10 ng/mL to 400 ng/mL for curcumin （average R2 = 0.997 2）. Excised nude mouse dorsal side skin was used in an in vitro skirt permeation study performed using the method of Franz. Results： Our results showed that all of the topical gel formulations we developed were free from skin irritation. The percutaneous flux and enhancement ratio of curcumin across nude mouse epidermis were enhanced markedly by the addition of menthol or Azone to both types of gel formulations. We found that the HPC gels containing quantities of Azone showed an enhanced permeation effect as compared to gels containing menthol. In the case of HPC gels containing Azone, the increase in permeability was significant （P〈0.05） as compared to the gels containing menthol. Conclusion： Azone shows a significantly more remarkable permeation effect than menthol. As such, this novel delivery strategy offers significant promise and is worthy of further exploration in attempts to enhance the medicinal application of curcumin