Active pharmaceutical ingredient Solubility

The Role of Solubility Modeling and Crystallization in the Design of Active Pharmaceutical Ingredients... 

The design of crystallization processes for the manufacture of Active Pharmaceutical Ingredients is a significant technical challenge to Process Research and Development groups throughout the Pharmaceutical and related industries. It requires an understanding of both the thermodynamic and kinetic aspects of crystallization, to ensure that the physical properties of the product will consistently meet specification. Failure to address these issues may lead to production problems associated with crystal size, shape and solubility, and to dissolution and bioavailability effects in the formulated product. 

The Committee for Proprietary Medicinal Products [8] applied the BCS, with certain requirements, to dispense with bioequivalency tests if the active pharmaceutical ingredient is class I and the in vitro dissolution of the finished dosage form is fast [9], An active substance is considered highly soluble if the amount contained in the HDS of an IR product is dissolved in 250 ml of each of three buffers within the range of pH 1-8 at 37°C (e.g., pH 1.0, 4.6, and 6.8). There should be linear and complete absorption, which indicates HP to reduce the possibility of an IR dosage form influencing the bioavailability [8], The similarity of the dissolution profiles of the test and reference products is demonstrated in each of three buffers within the range of pH 1-8 at 37°C (e.g., pH 1.0,4.6, and 6.8). If there is rapid dissolution of the product, where at least 85% of the active substance is dissolved within 15 min, no further comparison of the test and reference is required. Further requirements include that excipients be well established and have no interaction with the pharmacokinetics of the active substance and that the method of manufacture of finished product... 

The majority of active pharmaceutical ingredients on the market are small molecules derived from a synthetic route they are, partially badly, or not soluble in water. 

P.M. Bhatt, N.V. Ravindra, R. Banerjee, G.R. Desiraju, Saccharin as a salt former. Enhanced solubilities of saccharinates of active pharmaceutical ingredients, Chem. Comm. (2005) 1073-1075. 

By the time an active pharmaceutical ingredient (API) is made available to an analytical chemist in the formulation development group, most or all of the physical characteristics of an API has already been studied and the information should be available in some sort of a report from the drug substance group or preformulation group. Some of the key parameters that an analytical chemist in formulation development requires from such a report are the solubility and solution stability. 

Saccharin, acting as a weak acid, forms salts with basic active pharmaceutical ingredients and these salts have the desirable property of enhanced water solubility <2005CG1073>. 

An increasing need to work with active pharmaceutical ingredients (APIs) that have very low solubility in aqueous biological fluids. 

Prediction of Solubility of Active Pharmaceutical Ingredients in Single Solvents and Their Mixtures — Solvent Screening... 

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. 

Eligibility for the biowaiver procedure based on solubility and permeability characteristics of the active pharmaceutical ingredient... 

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