Dispersion formulation

As a result of the forces inherent in agglomerates, such as surface charges or mechanical interlocking of particles, the following problems are encountered in dispersion formulations. 

Modem oil spill-dispersant formulations are concentrated blends of surface-active agents (surfactants) in a solvent carrier system. Surfactants are effective for lowering the interfacial tension of the oil slick and promoting and stabilizing oil-in-water dispersions. The solvent system has two key functions (1) to reduce the viscosity of the surfactant blend to allow efficient dispersant application and (2) to promote mixing and diffusion of the surfactant blend into the oil film [601]. 

Each oil-dispersant combination shows a unique threshold or onset of dispersion [589]. A statistic analysis showed that the principal factors involved are the oil composition, dispersant formulation, sea surface turbulence, and dispersant quantity [588]. The composition of the oil is very important. The effectiveness of the dispersant formulation correlates strongly with the amount of the saturate components in the oil. The other components of the oil (i.e., asphaltenes, resins, or polar substances and aromatic fractions) show a negative correlation with the dispersant effectiveness. The viscosity of the oil is determined by the composition of the oil. Therefore viscosity and composition are responsible for the effectiveness of a dispersant. The dispersant composition is significant and interacts with the oil composition. Sea turbulence strongly affects dispersant effectiveness. The effectiveness rises with increasing turbulence to a maximal value. The effectiveness for commercial dispersants is a Gaussian distribution around a certain salinity value. 

Such a dispersant formulation for dispersing oil contains a mixture of a sorbitan monoester of an aliphatic monocarboxylic acid, a polyoxyethylene adduct of a sorbitant monoester of an aliphatic monocarboxylic acid, a water-dispersible salt of a dialkyl sulfosuccinate, a polyoxyethylene adduct of a sorbitan triester or a sorbital hexaester of an aliphatic monocarboxylic acid, and a propylene glycol ether as solvent [311,312]. 

Rodriguez Patino, J. M., Caro, A. L., Rodriguez Nino, M. R., Mackie, A. R., Gunning, A. P., and Morris, V. J. (2007). Some implications of nanoscience in food dispersion formulations containing phospholipids as emulsifiers. Food Client. 102, 532-541. 

During the past 30 years, there have been significant developments of parenteral disperse formulations. The use of parenteral emulsions can overcome the problems of low aqueous solubility and water hydrolysis of many drugs [184, 185]. Such formulations can avoid the use of conventional co-solvent systems and the undesirable effects caused by precipitation of drugs at the injection site. Recent developments of parenteral disperse formulations have the potential to provide sustained release and targeting of drugs [186-189],... 

Gonz ez, R.C.B. et al. (2002) Improved oral bioavailability of cyclosporin Ain male wistar rats comparison of a Solutol HS 15 containing self-dispersing formulation and a microsuspeihstoA. Pharm., 245 143-151. 

FIGURE 18.1 Advantages of a solid dispersion formulation, as compared to conventional capsule or tablet formulations, for enhancing dissolution rate, and consequent bioavailability of poorly water-soluble drugs. (From Serajuddin A. T. M. 19991 Pharm ScB8 1058-1066. With permission.)... 

Compared to conventional tablet and capsule dosage forms, solid dispersion formulations are relatively complex drug delivery systems, requiring a substantially greater commitment of time, effort, and resources fordevelopment. Therefore, whetherthere is a need forsolid dispersion and whetherthi... 

Another surface-active carrier useful for preparing solid dispersion formulations is tocopheryl polyethylene glycol 1000 succinate (TPGS)o0iR-tocopheryl PEG 1000 succinate (Eastman Chemical,... 

Fukumori, Y. Coating of multiparticulates using polymeric dispersions-formulation and process considerations, in Ghebre-Sellassie, I. (ed.), Multiparticulate Oral Drug Delivery. New York Marcel Dekker, 1994, pp. 79-111. 

More recently, Markovich et al. (91) utilized a combination of solid-state infra-red (IR) and NMR methods to study the amorphous to crystalline API transition of SCH 48461 in solid dispersion capsule formulations. In this illustrative study, dissolution testing initially revealed inter-and intralot variations of capsules stored under accelerated stability conditions (25°C/60% RH, 30°C/60% RH, and 40°C/80% RH). PXRD analysis could not explain the dissolution data being collected on lots stored at accelerated conditions and revealed no differences from original diffraction patterns. Two additional analytical techniques, attenuated total reflectance IR (ATR-IR) spectroscopy and solid-state 13C NMR spectroscopy, were employed to study the physical form in the actual solid dispersion formulations. 

The combination of solid-state ATR-IR and solid-state NMR data supported the conclusion that the presence of crystalline material was responsible for changes in the dissolution profiles of the different lots. The results appear consistent with historical examples of changes in API physical form of solid, high molecular weight, polyethylene glycol dispersion formulations of amorphous indomethacin and griseofulvin (92-95). 

Before detailing the accomplishments and recommending new directions, we make the general observation that applying and adapting the modeling tools that we possess now seems preferable to initiating effort on far more detailed chemical dispersion formulations. We have maintained a balanced posture in which the model advances and the improvements in measurements have kept pace with one another. 

The purpose of this section is to define the various parameters that are measured by DSC. The types of thermal events, exothermic or endothermic, that can be measured by DSC are reported in Table 1. The following sections will describe some of the more fundamental thermal events. Examples from the pharmaceutical field will be given to illustrate the techniques. The examples will be based on either single components such as drug substance and bulk excipients or on a mixture of components such as physical blends of drugs and excipients, solid dispersions, formulated drugs after granulation, and/or compression. 

Although for a true solution, the order in which solutes are added to the solvent is usually unimportant, this is not true for dispersed formulations. Because dispersed matter can distribute differently depending on the phase to which a particulate substance is added, the order of addition for these formulations is of critical importance. Any change in the order of addition, therefore, is a major change. 

Research was undertaken to develop a controlled release tablet of naproxen using ethylcellulose and both methods of wet granulation and solid dispersion were compared for effectiveness. Naproxen level was kept constant at 16% while ethylcellulose content was varied from 6% to 28% in the formulations. While both methods were successful at producing formulations with drug release profiles of at least 12 hours, the amount of ethylcellulose required to prepare such formulations was 33% less using the solid dispersion method. While none of the formulations released 100% of the drug, a cumulative 88% of naproxen was released from the solid dispersion formulation, compared with 84% from the wet granulation formulation (50). 

The degree of dispersion of a lipid-based delivery system appears to have the most marked effect on the bioavailability of a co-administered drug, and this has stimulated many of the most recent articles in the literature. Clearly, by decreasing the particle size of a dispersed formulation, the surface area available for lipid digestion and drug release or transfer is enhanced. In this regard, the bioavailability of griseofulvin [32, 33], phenytoin [23], penclomedine [30], dana-zol [34], REV 5901 [35], and, more recently, ontazolast [36] has been shown to be enhanced after administration in an emulsion formulation compared with a tablet, aqueous solution, or suspension formulation. It is not clear in these cases how much more efficient the emulsion formulation would have been compared with a simple lipid solution. 

---