Characterization of glass solutions of poorly water-soluble drugs produced by melt extrusion with hydrophilic amorphous polymers

Abstract

Indomethacin, lacidipine, nifedipine and tolbutamide are poorly soluble in water and may show dissolution-related low oral bioavailability. This study describes the formulation and characterization of these drugs as glass solutions with the amorphous polymers polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone-co-vinyl acetate by melt extrusion. The extrudates were compared with physical mixtures of drug and polymer. X-ray powder diffraction, thermal analysis, infrared spectroscopy, scanning electron microscopy, HPLC, moisture analysis and dissolution were used to examine the physicochemical properties and chemical stability of the glass solutions prepared by melt extrusion at a 1:1 drug/polymer ratio. Depending on the temperature used, melt extrusion produced amorphous glass solutions, with markedly improved dissolution rates compared with crystalline drug. A significant physico-chemical interaction between drug and polymer was found for all extrudates. This interaction was caused by hydrogen bonding (H-bonding) between the carbonyl group of the pyrrole ring of the polymer and a H-donor group of the drug. Indomethacin also showed evidence of H-bonding when physical mixtures of amorphous drug and PVP were prepared. After storage of the extrudates for 4-8 weeks at 25 degrees C/75% relative humidity (RH) only indomethacin/polymer (1:1) extrudate remained totally amorphous. All extrudates remained amorphous when stored at 25 degrees C/< 10% RH. Differences in the physical stability of drug/polymer extrudates may be due to differences in H-bonding between the components.

Improved dissolution of a poorly water soluble drug in solid dispersions with polymeric and non-polymeric hydrophilic additives

“…Hence, it can be inferred that IBS was present in the amorphous state in the dispersion and mannitol was in the crystalline state. Similar behavior has been reported for mannitol with other drug substances in earlier studies (14,17).…”

“…However, the glass transition event of this phase was observed at a temperature higher than the temperature expected based on the composition (Table I). Such an increase in T g has been observed previously as a result of ionic and heteromolecular interactions (14,19,20). Theoretical T g of the drug-additive mix (Table I) (1)…”

“…These »amorphous alloys« permit creation of custom pharmaceuticals with unique properties by selection of appropriate interacting excipients (12). Numerous reports have cited dissolution rate improvement of poorly soluble drugs through production of SDs using various hydrophilic carriers, such as polyvinylpyrrolidone, hydroxypropyl methylcellulose, sugars, and mannitol (13)(14)(15)(16). Dispersions of IBS were formed using two non-polymeric excipients, tartaric acid and mannitol, and two polymeric excipients, PVP and HPMC.…”

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

“…However, in this study, a co-amorphous dispersion was obtained at molar ratios of OL:ascorbic acid; 1:2 and 1:3 using rapid solvent evaporation under vacuum. The interaction between ascorbic acid and OL was effected most probably by H-bonding of the NH group of OL and the carbonyl group of ascorbic acid (Forster et al, 2001). In addition to its solubility enhancing effect in the prepared dispersions, ascorbic acid also is expected to provide antioxidant and neuroprotective effects to the final film formulation (Allahtavakoli et al, 2015;Xu et al, 2015).…”

Photostable Solid Dispersion of Nifedipine by Porous Calcium Silicate

“…8) Solid dispersions are generally prepared with water-soluble polymers as carriers. [9][10][11][12] Recently, porous materials have been used as carriers of solid dispersions. [13][14][15][16][17] The amorphous state undergoes more rapid photodegradation than the corresponding crystalline state.…”