Structure determination and characterization of carbendazim hydrochloride dihydrate

The objective of this study was to synthesize and characterize the hydrochloride salt of carbendazim with the aim of improving the intrinsic solubility of the parent compound. Carbendazim hydrochloride dihydrate was synthesized for the purpose of increasing the aqueous solubility of the parent drug, carbendazim. This was done with the commonly used saturation and cooling method. The structure was determined by single crystal radiograph crystallography, and the hydrochloride salt was found to be a dihydrate. The salt crystallized in a P 21 21 21 (#19) space group, which is typical for nonplanar, achiral, and noncentrosymmetric molecules. The asymmetric unit is comprised of 1 molecule each of carbendazim and chloride and 2 water molecules. The carbendazim molecules arrange themselves in a helical structure, with the waters and the chloride molecules in the channel linking the helix. The crystal lattice is held together by numerous hydrogen bonds, as well as van der Waals interactions. The melting point of the salt is 125.6°C. The solubility of the salt is 6.08 mg/mL, which is a thousand-fold increase from the intrinsic solubility (6.11 μg/mL) of the free base

Industrially feasible alternative approaches in the manufacture of solid dispersions: A technical report

The purpose of this report was to compile relevant technical information on various alternative strategies that can be used as feasible approaches in the development of solid dispersions. The technologies discussed in the report are spray coating on sugar beads with a fluidized bed coating system, hot melt extrusion, direct capsule filling, electrostatic spinning, surface active carriers, and supercritical fluid technology. The focus is on basic principles, the equipment involved, and the relevant scale-up work. These technologies have been found to eliminate several drawbacks posed by the conventional methods of manufacturing of solid dispersions such as laborious preparation methods, reproducibility, scaling up of manufacturing processes, stability of drug, and vehicle

Oral formulation of a novel antiviral agent, PG301029, in a mixture of Gelucire 44/14 and DMA (2∶1, wt/wt)

To develop an oral formulation for PG301029, a novel potent agent for the treatment of Hepatitis C virus infection, that not only has very low aqueous solubility but also degrades rapidly in water. The solubility of PG301029 was determined in water, various aqueous media, and several neat organic solvents. The stability of PG301029 was monitored at room temperature in buffess for 4 days, and in several neat organic solvents for up to 8 mo. Drug concentrations were measured by high-performance liquid chromatography (HPLC). Based on solubility and stability data, Gelucire 44/14 and DMA (N,N-dimethylacetamide) at a weight ratio of 2 to 1 were chosen as the formulation vehicle. After the vehicle was prepared, it was maintained in liquid form at ∼40°C until the PG301029 was dissolved. The final formulation product was a semisolid at room temperature. The bioavailability of the formulation was tested on 4 female BALB/c mice. PG301029 is insoluble in all tested aqueous media, while its solubility is promising in DMA. This compound is unstable in aqueous media and some organic solvents; however, it is stable in DMA. This proposed formulation is able to hold up to 10 mg/mL of drug and is stable at 4°C. The shelf life for this formulation stored at 4°C is extrapolated to be greater than 4 years. This formulation dramatically increases the bioavailability of PG301029. This nonaqueous formulation solves the stability, solubility, and bioavailability problems for PG301029. This semisolid formulation can easily be incorporated into soft elastic capsules

Solid Dispersion as an Approach for Bioavailability Enhancement of Poorly Water-Soluble Drug Ritonavir

Ritonavir is an antiretroviral drug characterized by low solubility and high permeability which corresponds to BCS class II drug. The purpose of the study was to develop solid dispersion by different methods and investigate them for in vitro and in vivo performance for enhancing dissolution and bioavailability, respectively. Since the drug possesses food-related absorption, the effect of biorelevant media (FaSSIF and FeSSIF state) on dissolution behavior was also studied. The solid dispersion was prepared using Gelucire as carrier in 1:4 ratio by different methods and were characterized for differential scanning calorimetry (DSC), X-ray diffractometry, scanning electron microscopy, and FT-IR. Oral bioavailability of 10 mg of ritonavir in solid dispersion prepared by solvent evaporation (SE1) and melt method (MM1) was compared with pure drug after oral administration of solid dispersion and pure drug to Albino Wistar rats of either sex. The results suggested formation of eutectic solid dispersion. In vitro dissolution studies was performed in 0.1 N HCl and biorelevant media showed enhanced dissolution rate as compared to pure drug in both FeSSIF media and 0.1 N HCl. The apparent rate of absorption of ritonavir from SE1 (Cmax 20221.37 ng/ml, tmax 0.5 h) was higher than that of MM1 (Cmax 2,462.2, tmax 1 h) and pure drug (Cmax 1,354.8 ng/ml, tmax 0.5 h). On the basis of the result obtained, it was concluded that solid dispersion is a good approach to enhance solubility and bioavailability of poorly water-soluble ritonavir