Hot-stage microscopy for determination of API fragmentation: comparison with other methods.

Although the fragmentation of the active pharmaceutical ingredient (API) is a phenomenon that is mentioned in many literature sources, no well-suited analytical tools for its investigation are currently known. We used the hot-stage microscopy method, already presented in our previous work, and studied the real fragmentation of the tadalafil particles in model tablets which were prepared under different compaction pressures. The morphology, spectral imaging and evaluation of plastic and elastic energies were also analyzed to support the hot-stage method. The prepared blend of tadalafil and excipients was compacted under a several forces from 5 to 35 kN to reveal the trend of fragmentation. The exact fragmentation of tadalafil with increased compaction pressure was revealed by the hot-stage microscopic method and it was in good agreement with plastic and elastic energies. Conversely, spectral imaging, which is being used for this analysis, was considered to be inaccurate methodology as mainly agglomerates, not individual particles, were measured. The availability of the hot-stage microscopic method equips pharmaceutical scientists with an in vitro assessment technique that will more reliably determine the fragmentation of the API in finished tablets and the behavior of the particles when compacted.

A new way of solid dosage form samples preparation for SEM and FTIR using microtome.

Rapid and correct production of generic solid dosage forms requires a large amount of analytical data and conclusions. Modern analytical techniques have a good resolution and accuracy and allow obtaining a lot of information about the original product. Scanning electron microscopy (SEM) is used for observation and assessing individual layers, core and surface of solid dosage forms. Fourier transform infrared (FTIR) spectroscopy mapping allows determining the distribution and characterization of individual components in a solid dosage form. However, the samples prepared by common way, using scalpel or tablet splitter, are not good enough. It was the reason for development of a new and better method of sample preparation, which uses microtome. Well-prepared samples analyzed by SEM and FTIR mapping allow to determine a solid dosage form formulation, excipient content and distribution of excipient and active pharmaceutical ingredient.

Preparation of candesartan and atorvastatin nanoparticles by solvent evaporation.

The solubility, absorption and distribution of a drug are involved in the basic aspects of oral bioavailability Solubility is an essential characteristic and influences the efficiency of the drug. Over the last ten years, the number of poorly soluble drugs has steadily increased. One of the progressive ways for increasing oral bioavaibility is the technique of nanoparticle preparation, which allows many drugs to thus reach the intended site of action. Candesartan cilexetil and atorvastatin, belonging to class II of the biopharmaceutical classification system, were chosen as model active pharmaceutical ingredients in this study. Forty samples were prepared either by antisolvent precipitation/solvent evaporation method or by the emulsion/solvent evaporation technique with various commonly used surface-active excipients as nanoparticle stabilizers. All samples were analyzed by means of dynamic light scattering. The particle size of the determined 36 nanoparticle samples was to 574 nm, whereas 32 samples contained nanoparticles of less than 200 nm. Relationships between solvents and excipients used and their amount are discussed. Based on the results the investigated solvent evaporation methods can be used as an effective and an affordable technique for the preparation of nanoparticles.

Primary investigation of the preparation of nanoparticles by precipitation.

The absorption, distribution, biotransformation and excretion of a drug involve its transport across cell membranes. This process is essential and influenced by the characteristics of the drug, especially its molecular size and shape, solubility at the site of its absorption, relative lipid solubility, etc. One of the progressive ways for increasing bioavaibility is a nanoparticle preparation technique. Cholesterol, cholestenolone and pregnenolone acetate as model active pharmaceutical ingredients and some of the commonly used excipients as nanoparticle stabilizers were used in the investigated precipitation method that was modified and simplified and can be used as an effective and an affordable technique for the preparation of nanoparticles. All 120 prepared samples were analyzed by means of dynamic light scattering (Nanophox). The range of the particle size of the determined 100 nanoparticle samples was from 1 nm to 773 nm, whereas 82 samples contained nanoparticles of less than 200 nm. Relationships between solvents and used excipients and their amount are discussed.

Hot-stage microscopy for determination of API particles in a formulated tablet.

Although methods exist to readily determine the particle size distribution (PSD) of an active pharmaceutical ingredient (API) before its formulation into a final product, the primary challenge is to develop a method to determine the PSD of APIs in a finished tablet. To address the limitations of existing PSD methods, we used hot-stage microscopy to observe tablet disintegration during temperature change and, thus, reveal the API particles in a tablet. Both mechanical and liquid disintegration were evaluated after we had identified optimum milling time for mechanical disintegration and optimum volume of water for liquid disintegration. In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs. Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs. Good agreement was obtained, thereby confirming the robustness of our methodology. The availability of such a method equips pharmaceutical scientists with an in vitro assessment method that will more reliably determine the PSD of active substances in finished tablets.