Water Insoluble Organic Solvents and Solids

A lipid-based oral formulation is used for water-insoluble drugs in cases where typical formulation approaches (i.e., solid wet granulation, solid dry granulation, water-soluble liquid in a capsule) do not provide the required bioavail-ability, or when the drug itself is an oily substance (e.g., dronabinol, ethyl icosapentate, indomethacin farnesil, teprenone, and tocopherol nicotinate). The water-insoluble solvents used in commercially available solubilized oral formulations include oleic...

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...

Brief History From CFCs to HFAs

The first metered dose inhaler, Medihaler EpiTM was introduced in 1956 by Riker Laboratories (3M Pharmaceuticals) for the management of asthma and COPD. The delivery device has been well accepted since that time, as evidenced by the annual production of over a half-billion units (McDonald and Martin, 2000). Since the introduction of the MDI, p-adrenergic agonists, anticholinergics, corticosteroids, and cromolyn compounds have been the staple of management for the commonly occurring lung...

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...

References

Theory of Protein Solubility. Methods Enzymol. 1985 114 49-77. Arakawa T, Kita Y, and Carpenter JF. Protein-solvent Interactions in Pharmaceutical Formulations. Pharm Res 1991 8(3) 285-291. Audus Kand Raub T (ed). Biological Barriers to Protein Delivery. Pharm. Biotech. Vol. 4. (KL Audus, TJ Raub, Eds), 1993. Avramopoulou V, Mamalaki A, Tzartos, and Socrates J. Soluble, Oligomeric, and Ligand-binding Extracellular Domain of the Human alpha 7 Acetylcholine Receptor...

Aggregates as Promiscuous False Positive HTS Hits

It has been observed that certain compounds appear as frequent hitters in HTS regardless of the biological target, especially when screened at higher than 10 J.M concentration. Figure 5 shows examples of promiscuous HTS hits McGovern et al., 2002 McGovern et al., 2003 McGovern and Shoichet, 2003 . These spurious hits have low potency at 1-10 J.M, noncompetitive and reversible inhibition, flat SAR and poor selectivity. The potency increases with incubation time, but decreases with higher enzyme...

PH Bile Salts and Proteins for Biorelevance pH Adjustment

The importance of the pH to mimic the physiological conditions has been introduced in the section on Physiological Relevance. It has been demonstrated that media buffered to a pH varying from 5 to 8 were compatible with the Caco-2 cell monolayer Palm et al., 1999 Neuhoff et al., 2003, 2005 . PAMPA models have even been shown to be compatible with a wider range of pH, i.e., from 4 to 10 Bermejo etal., 2004 . Yamashita and coworkers studied the effect of medium pH on the transport rate of several...

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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...