Classification of solid dispersions: correlation to (i) stability and solubility (ii) preparation and characterization techniques

Solid dispersion has been a topic of interest in recent years for its potential in improving oral bioavailability, especially for poorly water soluble drugs where dissolution could be the rate-limiting step of oral absorption. Understanding the physical state of the drug and polymers in solid dispersions is essential as it influences both the stability and solubility of these systems. This review emphasizes on the classification of solid dispersions based on the physical states of drug and polymer. Based on this classification, stability aspects such as crystallization tendency, glass transition temperature (T_g), drug polymer miscibility, molecular mobility, etc. and solubility aspects have been discussed. In addition, preparation and characterization methods for binary solid dispersions based on the classification have also been discussed.     

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation,characterization, in vitro,and in vivo study

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD₅₀). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.     

Effects of preparing techniques and aging on dissolution behavior of the solid dispersions of NF/Soluplus/Kollidon SR: identification and classification by a combined analysis by FT-IR spectroscopy and computational approaches

Context: Pharmaceutical solid dispersions are known to be seriously affected by issues of aging and processing.

Objective: This study investigated the spectral patterns in the solid dispersions (SD) of Nifedipine/Soluplus/Kollidon SR and the feasibility of the methodology in identification and evaluation of the solid dispersions.

Methods: The SD samples were prepared by hot melt extrusion (HMESD), solvent-evaporation (SESD), and fusion-cooling (FCSD). In order to distinguish the different SD samples, a combined analytical strategy by FT-IR spectrum, Raman spectrum, and computational approaches (PCA and HCA) were developed to investigate the spectral patterns of the solid dispersions. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), and dissolution test were employed as the reference characterization. The stability test under the accelerated condition was carried out to investigate the physical stability of the SDs.

Result: For the three prepared SDs, the evident differences on the dissolution behaviors and the trend of aging was observed. By means of the combined analytical strategy, the samples could be successfully identified in terms of their preparing techniques. The strength of hydrogen bonding interaction between NF and polymers decreased in the order of HMESD?>?SESD?>?FCSD. The results of the stability test indicated that the similarity factor f₂ value of dissolution profile decreased in the order of HMESD?>?SESD?>?FCSD. HMESD exhibited a tendency of minimal changing on both dissolution behavior and spectral patterns.

Conclusion: The combined strategy suggested the possibility for identification of specific SDs in quality control and prediction of their trends on the aging.     

Preparation of tetragonal zirconia powders by a solid state reaction: Kinetics, phases and morphology

Powders of tetragonal (t)ZrO₂ have been prepared by a solid state reaction between sodium metazirconate and sodium metaphosphate. The reaction temperatures and times have been varied between 450 and 550°C and 5 and 75 h, respectively. Zirconia powder, mostly in thet andt′ phases, is obtained. The yield of ZrO₂ powder increases monotonically with time at all reaction temperatures according to a phase boundary controlled kinetics. The fraction oft phase also increases with time at 450°C and 500°C but goes through a maximum at 550°C, the highest temperature employed. A maximum of 55% of the precursor monoclinic zirconia (used to prepare sodium meta zirconate) is converted tot phase at 500°C/75 h. The ZrO₂ powder consists of crystallites of size 9–25 nm agglomerated into particles having average size between 2 and 4μm. The agglomerates have a breaking strength of 100 MPa. A hydrothermal treatment is found to break the agglomerates into smaller sizes. Grinding the powder in a mortar and pestle converts only 12% of thet phase into monoclinic, indicating that substantial fraction of the tetragonal phase is the non transformable varietyt′. Heating experiments also confirm this.