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40 October 2014 Tablets & Capsules alternative, and low-viscosity HPCs can play a role [6]. The disintegra- tion times they provide are competi- tive with those of other excipients, and their excellent plasticity makes the ODF easy to handle. The disinte- gration time of ODFs depends on the solubility of the active ingredient and the viscosity of the HPC. For example, a 20 percent concen- tration of the SL grade of HPC in a 20-micron-thick, 2-by-3-centimeter strip has been shown to provide a good balance of tensile strength and disintegration time for ibuprofen. In fact, disintegration times of a poorly soluble active such as ibuprofen (sol- ubility = 0.049 milligram per milli- liter) can be made even shorter when certain additives, such as calcium car- bonate, are added to the HPC film. SSL is the lowest molecular-weight- grade of HPC available, and while it too can accelerate disintegration, it may not provide enough tensile strength when used with some actives. Increasing the viscosity of the SL grade may, however, provide the film with the appropriate tensile strength. In general, HPC can be used as a base material for ODFs but the choice of HPC grade depends on the active, and additives may be required. Solubility enhancement Solid dispersions. HPC is a semi- crystalline polymer with high molec- ular mobility and plasticity and is thus used in a variety of formulation techniques to improve the dissolution rate of poorly soluble actives [7, 8]. Low-viscosity grades of HPC have been shown to successfully incorpo- rate solid dispersions of BCS Class II chemical entities at a 3-to-1 polymer- to-drug ratio (by weight) by hot-melt mixing, spray drying, ball milling, and solvent evaporation. Typically, hot-melt mixing is done at 150° to 180°C. (Higher mixing temperatures can degrade the polymer.) HPC can be effectively used with actives whose melting points are within or slightly above this temperature range. Actives with significantly higher melting points, however, might experience incomplete amorphous conversions. For example, HPC can be used in quantitative amorphous conversions of carbamazepine (melting point = 205°C) but the transformation of phenytoin (melting point = 296°C) is largely incomplete. To improve the amorphous conversion yield of high- melting-point actives using HPC, ball-milling or dissolving the mixture in polar, volatile organic solvents— followed by solvent evaporation or spray drying—has been shown to be effective. Nano-dispersions. Low-viscosity HPC grades can stabilize relatively wettable BCS Class II compounds during wet media milling in order to minimize the aggregation of nano- particle actives [9, 10]. For actives that are less wettable, sodium dode- cyl sulfate (SDS) can be added to produce well-dispersed, stable nano- suspensions, even when the active load is very high. In fact, combining HPC and SDS makes nano-suspen- sions very stable, leading to faster dissolution and quicker redispersion. Conclusion HPC has versatile processing capabilities to manufacture tablets and films. For IR oral solid forms, special low-viscosity HPC polymers possess unique advantages that have demonstrated effective binding, film formation, and solubility enhance- ment, among other applications (twin-screw granulation, roller com- paction, film coating, etc.). To this end, improvements in tablet proper- ties, orally disintegrating products, and bioavailability have been shown. Special low-viscosity HPCs thus offer a means to design better IR oral dosage products as formulators strive to meet consumers' needs. T&C References 1. Sugisawa et al. Effect of Particle Size of Hydroxypropyl Cellulose as Dry-Mixing Binder on Properties and Drug Release of Tablet Prepared by High Shear Mixer Granulation Method. 2013 AAPS Annual Meet - The Original Silicified MCC Optimize tablet development and manufacture: • • • • • • ystalline Cellulose ocr Silicified Micr ystalline Cellulose oved content unif Impr p mity or VISIT US: 2014 AAPS Annual Meeting and Exposition BOOTH# 1223 November 3-5, 2014 San Diego Convention Center VISIT US: 2014 AAPS Annual Meeting and Exposition BOOTH# 1223 November 3-5, 2014 San Diego Convention Center