Modeling powder encapsulation in dosator-based machines: II. Experimental evaluation.

A theoretical model was previously derived to predict powder encapsulation in dosator-based machines. The theoretical basis of the model was discussed earlier. In this part; the model was evaluated experimentally using two powder formulations with substantially different flow behavior. Encapsulation experiments were performed using a Zanasi encapsulation machine under two sets of experimental conditions. Model predicted outcomes such as encapsulation fill weight and plug height were compared to those experimentally obtained. Results showed a high correlation between predicted and actual outcomes demonstrating the model's success in predicting the encapsulation of both formulations. The model is a potentially useful in silico analysis tool that can be used for capsule dosage form development in accordance to quality by design (QbD) principles.

Modeling powder encapsulation in dosator-based machines: I. Theory.

Automatic encapsulation machines have two dosing principles: dosing disc and dosator. Dosator-based machines compress the powder to plugs that are transferred into capsules. The encapsulation process in dosator-based capsule machines was modeled in this work. A model was proposed to predict the weight and length of produced plugs. According to the model, the plug weight is a function of piston dimensions, powder-bed height, bulk powder density and precompression densification inside dosator while plug length is a function of piston height, set piston displacement, spring stiffness and powder compressibility. Powder densification within the dosator can be achieved by precompression, compression or both. Precompression densification depends on the powder to piston height ratio while compression densification depends on piston displacement against powder. This article provides the theoretical basis of the encapsulation model, including applications and limitations. The model will be applied to experimental data separately.

Desolvation kinetics of sulfameter solvates.

Solvates are often encountered in pharmaceutical solids and knowledge of their physical stability is necessary for their effective formulation. This work investigates the solid-state stability of five structurally related solvates of sulfameter (5-methoxysulfadiazine) by studying the kinetics of their desolvation reaction with thermogravimetric analysis, both isothermally and nonisothermally. Desolvation kinetic analysis was done isothermally by conventional model-fitting and nonisothermally by the complementary method. Calculated kinetic parameters (model, A and E(a)) were compared and related to the crystal structure of these solvates. A relationship was established between desolvation activation energy from isothermal results and solvent size; the larger the solvent molecule, the higher its solvate's desolvation activation energy. The best fitting solid-state reaction model correlated to single crystal structural features of sulfameter-solvates where solvent molecules occupied cavities in the unit cell. Finally, it was found that kinetic parameters obtained isothermally and nonisothermally were at variance. Therefore, kinetic results obtained from one method may not be extended to results form the other.

Solid-state kinetic models: basics and mathematical fundamentals.

Many solid-state kinetic models have been developed in the past century. Some models were based on mechanistic grounds while others lacked theoretical justification and some were theoretically incorrect. Models currently used in solid-state kinetic studies are classified according to their mechanistic basis as nucleation, geometrical contraction, diffusion, and reaction order. This work summarizes commonly employed models and presents their mathematical development.

Basics and applications of solid-state kinetics: a pharmaceutical perspective.

Most solid-state kinetic principles were derived from those for homogenous phases in the past century. Rate laws describing solid-state degradation are more complex than those in homogenous phases. Solid-state kinetic reactions can be mechanistically classified as nucleation, geometrical contraction, diffusion, and reaction order models. Experimentally, solid-state kinetics is studied either isothermally or nonisothermally. Many mathematical methods have been developed to interpret experimental data for both heating protocols. These methods generally fall into one of two categories: model-fitting and model-free. Controversies have arisen with regard to interpreting solid-state kinetic results, which include variable activation energy, calculation methods, and kinetic compensation effects. Solid-state kinetic studies have appeared in the pharmaceutical literature over many years; some of the more recent ones are discussed in this review.

Complementary use of model-free and modelistic methods in the analysis of solid-state kinetics.

There are many methods for analyzing solid-state kinetic data. They are generally grouped into two categories, model-fitting and isoconversional (model-free) methods. Historically, model-fitting methods were widely used because of their ability to directly determine the kinetic triplet (i.e., frequency factor [A], activation energy [E(a)], and model). However, these methods suffer from several problems among which is their inability to uniquely determine the reaction model. This has led to the decline of these methods in favor of isoconversional methods that evaluate kinetics without modelistic assumptions. This work proposes an approach that combines the power of isoconversional methods with model-fitting methods. It is based on using isoconversional methods instead of traditional statistical fitting methods to select the reaction model. Once a reaction model has been selected, the activation energy and frequency factor can be determined for that model. This approach was investigated for simulated and real experimental data for desolvation reactions of sulfameter solvates.