Economical impact of plasma fractionation project in Iran on affordability of plasma-derived medicines.

In Iran all transfusion services are concentrated under authority of one public and centralized transfusion organization which has created the opportunity of using plasma produced in its blood centers for fractionation. In 2008 voluntary and non remunerated Iranian donors donated 1.8 million units of blood. This indicates a 25/1000 donation index. After responding to the needs for fresh plasma and cryoprecipitate each year about 150000 L of recovered plasma are reserved for fractionation. In an attempt to improve both blood safety profile and availability and affordability of plasma derived medicines, Iran's national transfusion service has entered into a contract fractionation agreement for surplus of plasma produced from donated blood by voluntary non remunerated donors. In order to ensure safety of product produced, Iran has chosen to collaborate with international fractionators based in highly regulated countries. The main objective of this study was to evaluate the impact of contract plasma fractionation on the affordability of the plasma derived medicines in Iran. During 2006-2008, Iran's contract fractionation project was able to produce 46%, 18% and 6% of IVIG, Albumin and FVIII consumed in Iran's market, respectively. In contrary to IVIG and Albumin, due to fairly high consumption of FVIII in Iran, the role of fractionation project in meeting the needs to FVIII was not substantial. However, Iran's experience has shown that contract plasma fractionation, through direct and indirect effects on price of plasma derived medicines, could substantially improve availability and affordability of such products in national health care system.

Preparation and characterization of ibuprofen microspheres.

Ibuprofen was microencapsulated with Eudragit RS using an o/w emulsion solvent evaporation technique. The effects of three formulation variables including the drug:polymer ratio, emulsifier (polyvinyl alcohol) concentration and organic solvent (chloroform) volume on the entrapment efficiency and microspheres size distribution were examined. The drug release rate from prepared microspheres and the release kinetics were also studied. The results demonstrated that microspheres with good range of particle size can be prepared, depending on the formulation components. The drug:polymer ratio had a considerable effect on the entrapment efficiency. However, particle size distribution of microspheres was more dependent on the volume of chloroform and polyvinyl alcohol concentration rather than the drug:polymer ratio. The drug release pattern showed a burst effect for all prepared microspheres due to the presence of uncovered drug crystals on the surface. It was shown that the release profiles of all formulations showed good correlation with the Higuchi model of release.

Particle size analysis of concentrated phospholipid microemulsions I. Total intensity light scattering.

Water-in-oil phospholipid microemulsions prepared from a constant total surfactant/cosurfactant concentration of 25 wt% at four different lecithin/alcohol weight ratios (Km of 1:1, 1.5:1, 1.77: 1, and 1.94:1) and containing water concentrations (or volume fractions) ranging from 2.0 to 26 wt% (or 0.04 to 0.26) have been examined at 298 K using total intensity light scattering. The data obtained were analysed using the hard-sphere model of Percus-Yevick, modified to account for the partitioning of the alcohol between the various phases. The light-scattering results showed that, regardless of the Km or the alcohol used, a minimum water concentration of at least 9 wt% was required for the formation of a microemulsion; although this value was reasonably constant for each of the alcohols investigated, there was a tendency for a slightly higher concentration of water to be required for microemulsion formation at higher Km values. Simple calculations suggested that a microemulsion was formed only when sufficient water was present to satisfy the hydration of both the phospholipid head groups and the hydroxyl groups of the cosurfactant associated with the droplet. At water concentrations lower than this minimum value, a cosolvent system was observed. In all systems above this minimum concentration, as the concentration of water increased, the size of the microemulsion droplets also increased. Surprisingly, however, there was little difference in the size of the microemulsion droplets obtained with the different alcohols, regardless of the Km, although for a particular alcohol there was some indication that the higher Km systems produced the slightly smaller droplets for an equivalent water concentration. There was also a suggestion that the more hydrophobic alcohols produced slightly smaller droplets than the more polar alcohols at the same Km.

Particle size analysis of concentrated phospholipid microemulsions II. Photon correlation spectroscopy.

The solvated droplet size of concentrated water-in-oil (w/o) microemulsions prepared from egg and soy lecithin/water/isopropyl myristate and containing short-chain alcohol cosurfactants has been determined using photon correlation spectroscopy (PCS). The effect of increasing the water volume fraction (from 0.04 to 0.26) on the solvated size of the w/o droplets at 298 K has been investigated at 4 different surfactant/cosurfactant weight ratios (Km of 1:1, 1.5:1, 1.77:1, and 1.94:1); in all cases the total surfactant/cosurfactant concentration was kept constant at 25% w/w. In the case of the microemulsions prepared from egg lecthin, the diffusion coefficients obtained from PCS measurements were corrected for interparticulate interactions using a hard-sphere model that necessitated estimation of the droplet volume fractions, which in the present study were obtained from earlier total intensity light-scattering (TILS) studies performed on the same systems. Once corrected for hard-sphere interactions, the diffusion coefficients were converted to solvated radii using the Stokes-Einstein equation assuming spherical microemulsion droplets. For both egg and soy lecithin systems, no microemulsion droplets were detected at water concentrations less than 9 wt% regardless of the alcohol and Km used, suggesting that at low concentrations of added water, cosolvent systems were formed. At higher water concentrations, however, microemulsion droplets were observed. The changes in droplet size followed the expected trend in that for a fixed Km the size of the microemulsion droplets increased with increasing volume fraction of water. At constant water concentration, droplet size decreased slightly upon increasing Km. Interestingly, only small differences in size were seen upon changing the type of alcohol used. The application of the hard-sphere model to account for interparticulate interactions for the egg lecithin systems indicated that the uncorrected diffusion coefficients underestimated particle size by a factor of slightly less than 2. Reassuringly, the corrected droplet sizes agreed very well with those obtained from our earlier TILS study.

Prediction of Phase Behavior in Microemulsion Systems Using Artificial Neural Networks

Preliminary investigations have been conducted to assess the potential for using (back-propagation, feed-forward) artificial neural networks to predict the phase behavior of quaternary microemulsion-forming systems, with a view to employing this type of methodology in the evaluation of novel cosurfactants for the formulation of pharmaceutically acceptable drug-delivery systems. The data employed in training the neural networks related to microemulsion systems containing lecithin, isopropyl myristate, and water, together with different types of cosurfactants, including short- and medium-chain alcohols, amines, acids, and ethylene glycol monoalkyl ethers. Previously unpublished phase diagrams are presented for four systems involving the cosurfactants 2-methyl-2-butanol, 2-methyl-1-propanol, 2-methyl-1-butanol, and isopropanol, which, along with eight other published sets of data, are used to test the predictive ability of the trained networks. The pseudo-ternary phase diagrams for these systems are predicted using only four computed physicochemical properties for the cosurfactants involved. The artificial neural networks are shown to be highly successful in predicting phase behavior for these systems, achieving mean success rates of 96.7 and 91.6% for training and test data, respectively. The conclusion is reached that artificial neural networks can provide useful tools for the development of microemulsion-based drug-delivery systems.