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.

Evaluation of strain-induced hydrophobicity of pharmaceutical blends and its effect on drug release rate under multiple compression conditions

“…An effective approach to formulate a drug product must consider both the physical properties of the raw materials and the effects of process conditions; some process variables, such as force during tableting, are obvious and well known, whereas others, such as the shear rate and the level of strain imposed on the blend, can be important, particularly because they are scale-dependent, but are less known 1,2 . Increase in strain during the blending process has been shown to increase lubricant homogeneity 3 .…”

“…It is known that the desired dissolution profiles can also vary with a change in manufacturing process, composition, and formulation variables 16–19 . Level of MgSt, impeller speed in the mixer, and composition of binders and fillers are some of the parameters that have been found to affect the desired drug release rates 2,20 . Thus, understanding the significance of lubricant distribution at various shear conditions may help develop a better drug formulation.…”

Formulation design of double-layer in the outer shell of dry-coated tablet to modulate lag time and time-controlled dissolution function: Studies on micronized ethylcellulose for dosage form design (VII)

“…Although Avicel is a minor disintegrant, a small amount of Avicel did not improve the disintegration of tablet. [18][19] However, the hydrophilic property of Avicel seems to improve the solvent penetration from the lateral surface of dry-coated tablets, leading to a shorter lag time than for tablets prepared by EC powder.…”

Exploration of novel co-processed multifunctional diluent for the development of tablet dosage form

“…The compressibility characteristic of microcrystalline cellulose (MCC) is reduced by wet granulation. Drug dissolution is reduced when MCC is used intra-granularly and the effect is more pronounced in the case of slightly soluble drugs[6]. The disadvantage with the use of extra-granular Avicel PH 102 is that it exhibits poor flow[7].…”