References

Benzalkonium Chloride Product Information. Sigma-Aldrich Inc., http www. (accessed 5 2006) Bot AI, Tarara TE, Smith DJ, Bot SR, Woods CM, and Weers JG. Novel lipid-based hollow-porous microparticles as a platform for immunoglobulin delivery to the respiratory tract. Pharm Res 2000 17(3) 275-283. Dellamary LA, Tarara TE, Smith DJ, Woelk CH, Adractas A, Costello ML, Gill H, and Weers JG. Hollow Porous Particles in Metered Dose Inhalers. it Pharm Res 2000 17 168-174. FDA, 21 CFR (2), Use of...

Lipid Containing Solubilizing Vehicles in Capsules Three Solubilizing Excipients

Ascending the level of complexity of lipid-based formulations are those that contain mixtures of three excipients. Typical examples of such combinations include 1) medium-chain triglycerides, PEG, and PG 2) TPGS, PEG 400, and PG 3) oleic acid, cremophor EL, and ethanol or PG 4) Polysorbate 20, PEG 400, and povidone 5) medium-chain mono and diglycerides, a-tocopherol, and povidone 6) medium-chain triglycerides, glycol esters of fatty acids, and aspartic acid. There are at least seven...

Biopharmaceutical Classification System BCS and the Developmental Classification System DCS and Their Implications

For a drug to be orally available, the compound must dissolve and be absorbed through the gut in such a way so as to generate adequate drug levels at the pharmacologically active site so that the desired action(s) is obtained in a reproducible manner (Yu, 1999). Retrospective studies in the late 1980's showed that > 40 of drug failures in development could be traced to poor biophar-maceutical properties namely, poor dissolution or poor permeability (Prentis et al., 1988). This situation has...

Lead Optimization High Throughput Screening Analysis

If a candidate is selected for further assessment, it is produced in amounts sufficient for high throughput evaluation and other experimentation to screen for potency against a selected target. In addition, solubility and permeability can be assessed using the same DMSO-haystack solutions used to assess activity, based on kinetic solubility analysis and permeability through immobilized artificial membranes (Hidalgo, 2001 Zhu et al., 2002 Stoner et al., 2004 Dehring et al., 2004 Avdeef, 2005 Box...

Excipients

In order to achieve appropriate levels of solubilization, dissolution rate and potentially supersaturation, excipients are required (Rowe et al., 2006 International Pharmaceutical Excipients Council 2006). Excipients are components of dosage forms which are included for a variety of reasons and are usually not directly associated with the pharmacological activity of the selected drug substance. Historically, excipients have comprised ingredients e.g., to mask or improve taste, to optimize...

InWell Sonication

High throughput in-well sonication has been applied to dissolve compounds that are insoluble in DMSO in 96, 384, and 1536 well formats (Oldenburg et al., 2005). Compounds that precipitated from DMSO stocks, due to either water uptake that reduced solubility or low instrinsic solubility that promoted crystallization, can be re-dissolved by low energy sonication. Sonication can accelerate compound dissolution in seconds and, in some cases, drive the solution to supersaturation, due to energy...

Units for the Expression of Solubility

A discussion of the thermodynamics and kinetics of solubility first requires a discussion of the method by which solubility is reported. The solubility of a substance may be defined in many different types of units, each of which represents an expression of the quantity of solute dissolved in a solution at a given temperature. Solutions are said to be saturated if the solvent has dissolved the maximal amount of solute permissible at a particular temperature, and clearly an un-saturated solution...

Diseased Compromised Skin and Solvent Selection

Numerous physiological factors in healthy and diseased skin can affect topical drug delivery and consequently formulation design. For example, neonatal skin is more permeable than adult skin and site to site variations in permeability are well known with genital tissue more permeable than that on the head and neck with arm and leg skin even less permeable. However, it is with compromised skin, found in many conditions where topical dosage forms are applied, where solvent selection can be...

Solvents Not Widely Used for Topical Preparations

While the above describes some of the more commonly used solvents for topical formulations, and emphasises those that appear in the FDA inactive ingredient guide (1996), the listing does not describe some of the solvents that are widely used in research studies of topical delivery. Dimethylsulphoxide (DMSO) and similar solvents such as dimethylacetamide (DMA) and dimethylformamide (DMF) are popular in these studies, but present problems. All three of these solvents penetrate well into human...

Methods for Measuring Protein Solubility

While the solubility of most small molecules can be determined by dissolving the solid bulk in volatile solvents, drying, and dissolving in various solutions until no further dissolution is observed, it is risky to expose protein solids to volatile solvents without protein denaturation or to generate pure protein solids in their native conformation that lack other excipients. Thus, protein solubility is generally determined by concentrating the protein solution until a phase change...

Dcv

Solubility of proteins in co-solvent and non-aqueous conditions. dipole moment. Some success with polar protic solvents and polar aprotic solvents suggested that solubility can be enhanced by dissolution in an organic vehicle with a high dielectric constant (Chin et al., 1994 Houen, 1996). Increasing the dielectric constant may increase solubility, but it may also decrease stability. In general, no single parameter predicted lysozyme solubility, but protic polar solvents and hydrophilic...

Strategies to Overcome Solubility Issues in Aqueous Media

Several strategies have been developed to overcome solubility issues in assay media (Table 4). These are discussed below. Optimization of Dilution Protocols Dilution protocols can affect the actual assay concentration. Even if the final target concentration and buffer composition are the same, different dilution procedures can generate different assay concentrations. Table 5 shows an example with the same final target concentration, but with different dilution protocols. In the first protocol,...

Oils and Waxes

Mineral oil liquid paraffin and light mineral oil light liquid paraffin are widely used components of topical formulations such as emulsions, creams, lotions and ointments as well as other preparations such as baby lotions, sunscreens and cosmetics, and they provide cost effective solvents. Typically incorporated at up to 15 in lotions but at levels up to 95 in ointments, mineral oils comprise a complex mixture of branched alkanes also termed paraffinics and alkylated saturated ring compounds...

Biowaiver Injectable Gras

Predicting the Impact of Physiological and Biochemical Processes on Oral Drug Absorption. Adv DrugDeliv Rev 2001 50 S41-S67. Akers MJ. Excipient-Drug Interactions in Parenteral Formulations. J Pharm Sci 2002 91 2283-2300. Akkar A and M ller RH. Intravenous Itraconazole Emulsions Produced by SolEmuls Technology. EurJ Pharm Biopharm 2003 56 29-36. Amidon GL, Lennernjis H, Shah VP, and Crison JR. Theoretical Basis for a Bio-pharmaceutical Drug Classification The...