Solubility, dissolution

Avdeef, A., Voloboy, D., Foreman, A. Dissolution-solubility of multiprotic drugs pH, buffer, salt, dual-solid, and aggregation effects. In ADME/Tox Approaches, Van de Waterbeemd, H ... 

Thus, %F is defined as the area under the curve normalized for administered dose. Blood drug concentration is affected by the dynamics of dissolution, solubility, absorption, metabolism, distribution, and elimination. In addition to %F, other pharmacokinetic parameters are derived from the drug concentration versus time plots. These include the terms to describe the compound s absorption, distribution, metabolism and excretion, but they are dependent to some degree on the route of administration of the drug. For instance, if the drug is administered by the intravenous route it will undergo rapid distribution into the tissues, including those tissues that are responsible for its elimination. 

Dissolution (Solubility) Stability Permeability First pass... 

Jurgenliemk G, Nahrstedt A. Dissolution, solubility and cooperativity of phenolic compounds from Hypericum perforatum L. in aqueous systems. Pharmazie 2003 58 200-203. 

Dissolution, solubility, and permeability are the three fractors that control the bioavailability of a drug for an IR drug product. Provided the inactive excipient... 

May H.M., Kinniburgh D.G., Helmke P.A. and Jackson M.L. (1986) Aqueous dissolution, solubilities and thermodynamic stabilities of common aluminosilicate clay minerals Kaolinite and smectites. Geochim. Cosmochim Acta 50, 1667-1677. 

Is the particte size critical to dissolution, solubility or bioavailability ... 

BCS Class II Low-solubility, high-permeability drugs. These drugs are the main scope of this chapter. In general, BCS Class II drug products are likely to be limited by the dissolution/solubility rate. 

With very few exceptions, dissolution of the drug substance in the GI tract milieu is a prerequisite for drug absorption following oral administration. For Class II compounds, the rate-limiting factor in their intestinal absorption is dissolution /solubility [23-25]. Hence, in-depth understanding of this process is essential in the oral delivery of low-solubility compounds. Factors governing the dissolution process can be directly identified from the following equation, based on the Nernst-Brunner and Levich modifications of the Noyes-Whitney model [26-28] ... 

The BCS is a scientific framework for classifying active pharmaceutical ingredients based upon their aqueous solubility and intestinal permeabihty. When combined with the dissolution of the pharmaceutical product, the BCS takes into account three major factors that govern the rate and extent of drug absorption (exposure) from immediate-release oral solid dosage forms dissolution, solubility, and intestinal permeability. 

The biopharmaceutical information gathered in the candidate drug selection process regarding the characteristics of the drug molecule (e.g., dissolution, solubility, stability in fluids at the site of administration, enzymatic stability, membrane transport and bioavailability) is also very useful as input to the subsequent formulation development. This information is important, for example,... 

Will the drug absorption be limited by the drug dissolution/solubility ... 

Will the drug dissolution/solubility limit the bioavailability to an extent that endangers the clinical usefulness of the drug ... 

Additional solid-state techniques are covered in the chapter on solid-state analysis and polymorphism. The determination and control of the solid-state form, in respect of both crystal structure and particle characteristics, are important. The physical properties of the dmg substance will influence its behaviour during handling processes and formulation, and can have a dramatic effect on dissolution, solubility and therefore bioavailability. 

API and polymer dissolution Solubility and stability in solvent Temperature and time Solid content and viscosity Mixer design and speed... 

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