LogP/LogD/pKa/pH Solubility in Preformulation Analysis

Partition coefficient (Log P), distribution coefficient (Log D), Ionization constant (pKa) and pH solubility, the important components of inherent properties of drug substances and inactive ingredients, can determine the physicochemical properties, quality and potency of the end products. A good compound, which has a favorable hydrophile-lipophile balance (HLB), not only able to permeate across biological membranes such as the intestine wall, but also dissolve to blood/plasma and other aqueous bodily fluids. In this case, an early investigation of these inherent physicochemical characteristics is highly desirable in the early stage of drug discovery and formulation development to find out a valuable lead candidate and viable vehicles.

Alfa Chemistry can apply a suit of advanced techniques to help you with determination of the compound's division between water and octanol phases. Additionally, solubility analysis will be investigated in PBS at various pH values and the pKa testing will be performed by our analysts through calculating the logP or logD values and measured in various pH values.

Lipophilicity (LogP/LogD)

Although a high enough water solubility is significantly important for a drug candidate especially for those aimed for oral dosing, an appropriate lipophilicity, determined by the dissolving capacity of compounds in lipohilic (non-aqueous) solutions, is required for these substances to permeate through various biological membrane. For evaluating lipophilicity of a compound, logP is an important parameter which is measured as the compounds distribution between non-aqueous (octanol) and aqueous (water) phase. It is widely accepted that a desired logP value should be no more than 5 that means 1:100,000 concentration difference between water and octanol phases. LogD, generally termed as distribution coefficient, is another common measure for lipophilicity. Since the determination of an object's logD is closely related to the compounds ionized and non-ionized forms, thus various pH conditions are evolved in the measurement.

At Alfa Chemistry , your requirements for logP/logD evaluation can be satisfied with timeliness and cost-effectiveness. Besides using the 'gold standard' methods UPLC-UV or MS quantitation for measuring your product's logP/logD, our highly trained analysts can assist you to optimize the development strategy for supporting your drug discovery program.

pKa

pKa, commonly defined as the acid dissociation constant at logarithmic scale, represents a measurement of the strength of the acid. Recognizing the fact that all of the drug substances are almost weak acids or bases, a deeply understanding of the pKa value for your drug candidates may contribute to a prediction for the end product's performance, which are valuable to the progress of your pharmaceutical program. Accumulating evidences have demonstrated that pKa values play a significant role in influencing various behavior of compounds including absorption, binding with targeted site, salt form as well as certain important physicochemical properties such as lipophilicity, solubility and even the end products' dissolution. Your compound's pKa value will be analyzed under different pH values (ranging from pH 2 to pH 10) through our UV-metric methods and pH-metric methods. Finally, a comprehensive analytical report will be provided by our staff and you can contact with our experts for any further information about your assessment details and development advices.

pH Solubility

In general, the absorption rate of active substance, especially for the solid dosage from, is mainly determined by the dissolution phase of the drug formulations. However, the dissolution profile of API contained in an end drug product can be significantly influenced by the pH values in vivo. Given the fact that the pH values vary in different bodies and organs such as stomach (1.0-3.0), small intestine (6.5-7.0) and large intestine (8.4-8.55), determination of the solubility profile of an active substance is critical to prediction of the product's bioavailability and pharmacological action in vivo. By collecting and subsequently analyzing these important parameters, we can determine the drug development strategy and optimize the molecule structure, crystal/salt form and other properties of the drug compounds.

At Alfa Chemistry , we provide customers a comprehensive solubility analysis under different pH conditions through the pH-metric solubility assay. Such method is mainly based on the investigating the small range of pH changes in a solution where an ionizable compound precipitates or dissolves.

From such examination, we can obtain parameters include as follows:

• Kinetic solubility (SK) of the neutral species

• Intrinsic solubility (So) of the neutral species

• pH-solubility profile according to Henderson-Hasselbalch equations

• Extent and duration of supersaturation

Alfa Chemistry have decades of experience in analyzing the common physicochemical properties of various compounds and our scientists will conduct these analysis depending on our customer's needs. With highly efficient work flows and extensive expertise, we are capable of providing a full range of analysis services and comprehensive reports with high standard quality and cost-effectiveness.

References

• Bharate, S. S., Kumar, V. and Vishwakarma, R. A. (2016) 'Determining Partition Coefficient (Log P), Distribution Coefficient (Log D) and Ionization Constant (pKa) in Early Drug Discovery'. Comb Chem High Throughput Screen, 19(6): 461-469.

• Ashford, M. and Fell, J. T. (1994) 'Targeting drugs to the colon: delivery systems for oral administration'. J Drug Target, 2(3):241-57.