Therapeutic proteins as biopharmaceuticals have emerged as a very important class of drugs for the treatment of many diseases. However, they are less stable compared to conventional pharmaceuticals. ...Their long-term stability in solid forms, which is critical for product performance, depends heavily on the retention of the native protein structure during the lyophilization (freeze-drying) process and, thereafter, in the solid state. Indeed, the biological function of proteins is directly related to the tertiary and secondary structure. Besides physical stability and biological activity, conformational stability (three-dimensional structure) is another important aspect when dealing with protein pharmaceuticals. Moreover, denaturation as loss of higher order structure is often a precursor to aggregation or chemical instability. Careful study of the physical and chemical properties of proteins in the dried state is therefore critical during biopharmaceutical drug development to deliver a final drug product with built-in quality that is safe, high-quality, efficient, and affordable for patients. This review provides an overview of common analytical techniques suitable for characterizing pharmaceutical protein powders, providing structural, and conformational information, as well as insights into dynamics. Such information can be very useful in formulation development, where selecting the best formulation for the drug can be quite a challenge.
A general review of the methods available for the physical characterization of pharmaceutical solids is presented. The techniques are classified as being on the molecular level (properties capable of ...being detected in an ensemble of individual molecules), the particulate level (properties which can be detected through the analysis of an ensemble of particles), and the bulk level (properties which can be measured only using a relatively large amount of material). The molecular-level properties discussed are infrared spectroscopy and nuclear magnetic resonance spectrometry, the particulate-level properties discussed are particle morphology, particle size distribution, powder X-ray diffraction, and thermal methods of analysis, and the bulk-level properties discussed are surface area, porosity and pore size distribution, and powder flow characteristics. Full physical characterization of three modifications of lactose (hydrous, anhydrous, and Fast-Flo) is presented to illustrate the type of information which can be obtained using each of the techniques discussed.
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Eutectic mixtures have been known for a long time in the pharmaceutical field. However, its potential as a system to improve the solubility and dissolution of poorly water-soluble ...drugs remains little explored. Studies involving the microstructural characterization and the preparation of solid dosage forms containing eutectic mixtures are also an issue to be developed. Recently, the number of studies involving the preparation of eutectic mixtures to improve the solubility and oral bioavailability of poorly soluble drugs has increased considerably, including drug-carrier and drug-drug mixtures. In this review is discussed the potential of eutectic mixtures as an alternative pharmaceutical solid system to enhance drugs solubility, dissolution rate or oral bioavailability. Different aspects like history, physico-chemical, microstructural properties, preparation methods, mechanisms involved in solubility/dissolution enhancement, techniques for solid state characterization, in vivo studies, advantages, limitations and formulation perspective are also discussed.
Theoretical equations for the prediction of moisture sorption of pharmaceutical preparations under various conditions were derived and evaluated. They are useful for the design of moisture-proof ...packaging and the quality assurance of pharmaceutical preparations, as moisture sorption is one of the factors which affect physical properties, appearance, and chemical stability of pharmaceutical preparations. Moisture sorption under the shelf condition can be predicted accurately when the temperature change, relative humidity change, moisture sorption isotherm, activation energy of permeability, and heat of vaporization are taken into consideration. A method for the estimation of moisture sorption rate constant of pharmaceutical preparations is also described. Experiments were carried out for moisture sorption of packaged salt, plain tablets, or sugar-coated tablets under various conditions, and it was proved that calculated values were in good agreement with the observed values.
Abstract The objective of this paper was to develop and evaluate two semi-solid pharmaceutical forms containing 0.1% tacrolimus: cream (CRT01) and gel (GLT01). For the evaluation of physicochemical ...stability, at times 0, 30, 60 and 90 days, at 23°C and at 40°C, High Performance Liquid Chromatography coupled with a Diode Array Detector (HPLC-DAD) was employed. This method was developed and validated for tacrolimus quantification. The occlusivity test and skin permeation assay were also performed, using an animal model (Wistar rats), and the CRT01 and GLT01 were compared to the 0.1% tacrolimus ointment (PFU01) obtained from the University Pharmacy, Federal University of Rio de Janeiro, Brazil. CRT01 and GLT01 presented a homogeneous aspect and consistency adequate for topical products, along with sensory characteristics above PFU01. They also presented adequate physicochemical stability for 90 days and a lower occlusive effect than PFU01 (p<0.05). CRT01 showed greater affinity for the skin when compared to PFU01 and GLT01, with low systemic absorption. The CRT01 semi-solid formulation was considered the most adequate one to treat patients with atopic dermatitis or other dermatologic inflammatory diseases, promoting rational use of tacrolimus.
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Magnesium stearate (Mg-St) is a common lubricant used for solid pharmaceutical formulations and is known for its property to cause delay of tablet dissolution. In this study, the ...mechanism underlying the delay caused by Mg-St was investigated with model metformin hydrochloride (HCl) tablets containing Mg-St by using the stationary disk method, scanning electron microscopy with energy dispersive X-ray spectrometry (SEM-EDS), and Fourier transform infrared spectroscopy (FTIR). The results revealed the process and mechanism of delay: the exposed amount of Mg-St on the tablet surface increases during the dissolution process, and tablet dissolution is limited by the diffusion of Mg-St. In addition, in the case of dissolution in acidic medium, stearic acid derived from Mg-St was detected on the tablet surface by FTIR. Because the solubility of stearic acid is lower than that of Mg-St, the slower dissolution in acidic medium than in neutral medium may be attributed to the generation of stearic acid.
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