title: The role of intra- and extragranular microcrystalline cellulose in tablet dissolution.
abstract: The objective of this study was to examine the influence of intra- and extragranular microcrystalline cellulose (MCC) on drug dissolution from tablets made by high-shear granulation. Granulations were made in a Littleford Model W-10-B (10-liter) mixer and dried in a fluid bed dryer (Niro Inc.). A Plackett-Burman screening design and 2(3) factorial design were employed to study how drug type, MCC (intra- or extra-), filler type (lactose or dicalcium phosphate), disintegrant type (sodium starch glycolate or croscarmellose sodium) and level, proportion of magnesium stearate, and impeller speed affect tablet hardness, disintegration time, and dissolution. Two model drugs were chosen based on their solubility: metoprolol tartrate (solubility > 1000 mg/ml) and hydrochlorothiazide (solubility = 1.05 mg/ml). Tablets were compressed to the same target weight (dose) and similar tablet hardness. In some cases, dissolution testing was also carried out on the loose granules. The intra-extragranular distribution of MCC was found critical to the compactibility and initial dissolution rates from these tablets. Intragranular MCC reduced drug dissolution, the effect being most marked in the case of the slightly soluble hydrochlorothiazide. For formulations containing intragranular MCC, the granulating fluid level on tablet dissolution was also important, since an increase in fluid level resulted in slower drug dissolution from both the loose granules and the tablets compressed from them. Conversely, extragranular MCC tended to increase both dissolution rates and compactibility. It may be concluded that the appropriate distribution of MCC between and within granules may optimize both dissolution and compactibility without changing overall tablet composition.
authors.affiliation: University of Maryland at Baltimore, Department of Pharmaceutical Sciences, School of Pharmacy 21201-1180, USA.
authors.forename: J Z
authors.initials: JZ
authors.lastname: Li
authors.forename: G S
authors.initials: GS
authors.lastname: Rekhi
authors.forename: L L
authors.initials: LL
authors.lastname: Augsburger
authors.forename: R F
authors.initials: RF
authors.lastname: Shangraw
mesh_terms: D002482:Cellulose / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations; D004232:Diuretics; D005079:Excipients / Q000737:chemistry*; D006852:Hydrochlorothiazide / Q000737:chemistry; D011208:Powders; D049993:Sodium Chloride Symporter Inhibitors / Q000737:chemistry; D012995:Solubility; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D004232:Diuretics; D005079:Excipients; D011208:Powders; D049993:Sodium Chloride Symporter Inhibitors; D013607:Tablets; D006852:Hydrochlorothiazide; D002482:Cellulose; C109691:microcrystalline cellulose