Deformation Potential and Tensile Strength of Tablets of a Dry Granulated Formulation.

The increase in solid fraction (SF) of a packed granule bed with pressure applied during the in-die compression process results in an evolution of the tablet's matrix and mechanical strength. In this case study, the tensile strength (TS) of a dry granulated microcrystalline cellulose (MCC)/mannitol (MNT)-based formulation was modeled in light of the deformation potential, ∆ (tablet SF - initial granule bed SF). Results showed that the TS of tablets linearly decreased as SF of granules (produced as mini-tablets of an ibuprofen formulation) increased.

Reproducibility of the Measurement of Bulk/Tapped Density of Pharmaceutical Powders Between Pharmaceutical Laboratories.

The bulk properties of a powder are dependent on the preparation, treatment, and storage of the sample, that is, how it was handled. The particles can be packed to have a range of bulk densities and, moreover, the slightest disturbance of the powder bed may result in a changed bulk density. Thus, the bulk density of a powder is often difficult to measure with good reproducibility and, in reporting the results, it is essential to specify how the determination was made.

Dropwise Additive Manufacturing of Pharmaceutical Products Using Particle Suspensions.

The principal method of drug delivery is by oral solid doses, the production of which often necessitates multiple post-crystallization unit operations to ensure content uniformity or enhance bioavailability. As an alternative to conventional dose production methods, applications of additive manufacturing technologies based on solvent- or melt-based formulations have demonstrated the potential for improvements to process efficiency, flexibility, and dosing precision. Here we explore the use of particulate suspensions in a dropwise additive manufacturing process as a method for dosing active ingredients in crystalline form, which may be difficult to achieve via powder processing due to poor flow properties.

Tablet Compression Force as a Process Analytical Technology (PAT): 100% Inspection and Control of Tablet Weight Uniformity.

The modern rotary pharmaceutical tablet press is capable of accepting or rejecting individual tablets based on the measured compression force of the tablet. Because during steady operation, each tablet is compressed to the same thickness, a larger compression force implies a heavier tablet. Tablets that are too heavy likely contain more than the desired content of drug substance.

Assessment of Intragranular and Extragranular Fracture in the Development of Tablet Tensile Strength.

When a tablet is compacted from deformable granules and then broken, the fracture plane may cleave granules in 2 (intragranular fracture) or separate neighboring granules (extragranular fracture). In this study, a novel method was developed to quantify the extent of intragranular versus extragranular fracture by compacting tablets from multicolored ideal granules and evaluating fracture surfaces. The proportions of intragranular and extragranular fracture were quantified and modeled in light of a new metric; the deformation potential, Δ, reflecting the solid fraction increase as an initial granule bed is compressed into a final tablet.

Note on the Use of Diametrical Compression to Determine Tablet Tensile Strength.

The diametrical compression (DC) test, as defined in United States Pharmacopeia <1217> and in American Society for Testing and Materials testing standard D 3967, has been used extensively to derive the tensile strength (TS) of pharmaceutical tablets from the measured breaking force. DC-derived TSs provide a good approach to measuring the consistency of tablet mechanical properties from one batch to the next. For these quality control type applications, method precision is required, but accuracy is not.

A first-principles model for prediction of product dose uniformity based on drug substance particle size distribution.

The unit dose uniformity (UDU) of low-dose drug products can be affected by active pharmaceutical ingredient (API) particle size. UDU relative standard deviation increases as the fraction of large API particles increases and/or as the unit dose decreases. Control of API particle size has traditionally been based on the empirical relationship of d(90) and/or d(50) statistics to drug product uniformity.

Using a novel multicompartment dissolution system to predict the effect of gastric pH on the oral absorption of weak bases with poor intrinsic solubility.

A novel multicompartment dissolution system was developed by modifying a conventional six-vessel United States Pharmacopoeia dissolution system to study the dissolution and possible precipitation of poorly soluble weak bases after oral administration. The modified system includes a "gastric" compartment, an "intestinal" compartment, an "absorption" compartment, and a reservoir to simulate the dissolution and absorption in the gastrointestinal tract. Dissolution profiles of 50-mg dipyridamole (pK(a) 6.

In situ monitoring of wet granulation using online X-ray powder diffraction.

Purpose: Polymorphic transformations during the wet granulation of a metastable polymorph of flufenamic acid were monitored in situ using online X-ray powder diffraction. The resulting data were used in testing a proposed process induced transformation rate model, which allows the extent and occurrence of polymorphic transformations during wet granulation to be controlled by adjusting the granulation time.

Methods: A small-scale, top mixing granulator was designed for compatibility with novel X-ray powder diffraction equipment (available from X-Ray Optical Systems of East Greenbush, NY).