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

Abstract

Aqueous solubility of a drug can be a critical limitation to its oral absorption. Lipophilic molecules, especially those belonging to the biopharmaceutics classification system (BCS) class II and IV, dissolve slowly, poorly and irregularly, and hence pose serious delivery challenges, like incomplete release from the dosage form, poor bioavailability, increased food effect, and high inter-patient variability (1). Many solubilization techniques have been described that either change the nature of the solvent environment (co- Irbesartan (IBS) is a hydrophobic drug with poor aqueous solubility and dissolution rate. Solid dispersions (SDs) of IBS were prepared with both small molecules (tartaric acid and mannitol) and polymeric additives (polyvinylpyrrolidone, PVP, and hydroxypropyl methylcellulose, HPMC). A 9.5 and 7 folds enhancement in solubility over the crystalline form (14.6 mg mL -1 ) was observed for tartaric acid (138 mg mL -1 ) and PVP (103 mg mL -1 ), respectively. Powder X-ray diffraction confirmed that IBS existed in the glassy state in all cases, even with excipients having low glass transition temperature. Thermal methods (differential scanning calorimetry and hot stage microscopy) were used to evaluate the miscibility of the drug and additives. These techniques suggested that tartaric acid led to generation of »amorphous solutions« in contrast to »amorphous suspensions« in other three cases.The in vitro dissolution of IBS depended on the additive load and increased with increasing concentration in the case of tartaric acid, an acidifying excipient. The results indicate the suitability of even small molecules for providing solubility benefits, which can be attributed to the good glass forming ability and reasonable ability of IBS to remain in the glassy state.

Multicomponent Amorphous Nanofibers Electrospun from Hot Aqueous Solutions of a Poorly Soluble Drug

“…SDS is often used as a transmembrane/transdermal enhancer, and mannitol is a sweetener often used for taste masking in oral formulations. The three excipients have good compatibility with each other, and PVP and SDS are often used to improve solubility of poorly soluble drugs (25,26). This suggested that the combined usage of PVP and SDS at an elevated temperature might improve the solubility of helicid synergistically (27,28).…”

Physicochemical characterization of artemether solid dispersions with hydrophilic carriers by freeze dried and melt methods

“…Artemether solubility was increased 15-fold depending on the concentration of an MPEG-LysinediFMOC (di-Fluorene methoxycarbonyl)-based dendrimeric nanoparticle carrier (Bhadra et al, 2005). Melting combines physical mixtures of drugs with water-soluble carriers to create solid dispersion systems (Sekiguchi and Obi, 1961) for dienogest (Dittgen et al, 1995A), Irbesartan (Chawla and Bansal, 2008), ketoconazole (Heo et al, 2005), nifedipine (Zajc and Srcic, 2004), nitrendipine (Wang et al, 2005), progesterone, and testosterone (Dittgen et al, 1995b(Dittgen et al, , 1995c. Melting only briefly subjects the drug/carrier matrix to high temperatures, allowing thermolabile to be processed.…”

Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan

“…[1] Different formulation approaches like solid dispersion and complexation with cyclodextrins have been already utilized to resolve the poor aqueous solubility of irbesartan (IRB). [23] Indeed, in some selected cases, these approaches have been successful, but they offer many other disadvantages like, in solid dispersion, the amount of carriers used is often large and, thus, if the dose of the active ingredient is high, the tablets or capsules formed will be large in volume and difficult to swallow. Moreover, because the carriers used are usually expensive and the freeze or spray-drying method requires particular facilities and processes, this leads to a high production cost.…”

“…Lipid-based drug delivery systems have gained considerable interest after the commercial success of Sandimmune Neoral (Cyclosporine A), Fortovase (Saquinavir) and Norvir (Ritonavir). [3–6]…”