pH Adjustment and Co-Solvent

pH Adjustment and Co-Solvent

The solubilization of poorly soluble drugs is a frequently encountered challenge in screening studies of new chemical entities as well as in formulation design and development. Orally administered drugs can only be completely absorbed when they show fair solubility in gastric medium and such drugs show good bioavailability. Bioavailability depends on several factors, drug solubilization in an aqueous environment and drug permeability through lipophillic membranes being the important ones. However, more than 40% NCEs (new chemical entities) developed in Pharmaceutical Industry are practically insoluble in water. These poorly water-soluble drugs are allied with slow drug absorption leading to inadequate and variable bioavailability and gastrointestinal mucosal toxicity. Therefore, the improvement of drug solubility, namely its oral bio-availability, remains one of the most challenging aspects of drug development process especially for oral drug delivery system.

Our approaches to drug solubilization

pH adjustment

There is sufficient evidence that pH changes in the gastrointestinal tract have an impact on drug bioavailability. By pH adjustment, poorly water-soluble drugs and some molecules that can be protonated (base) or deprotonated (acid) may potentially dissolve in water. Not only is pH adjustment a key parameter in pre-formulation, it is also important to use pH-altering excipients in drug delivery systems. Therefore, pH adjustment is a good technique for assessing the efficacy of poorly soluble drugs before clinical practice. Advantages:

  • Universality and relative simplicity
  • Simple to formulate, analyze, produce and fast track
  • Use a small amount of compound
  • Amenable to high throughput evaluations
  • For oral and parenteral administration
  • Increase the fraction of oral absorption drugs
  • Combine with co-solvent to increase the solubility of poorly soluble drugs
  • For crystalline and lipophilic poorly soluble compounds

Reduction of the dielectric constant is possible by the addition of co-solvents, which facilitates increased solubility of non-polar drug molecules. In order to maximize the solubility and prevent precipitation upon dilution, co-solvents are used in conjunction with surfactants and pH modifiers. Most co-solvents have hydrogen bond donor and/or acceptor groups as well as small hydrocarbon regions. Their hydrophilic hydrogen bonding groups ensure water miscibility, while their hydrophobic hydrocarbon regions interfere with the water hydrogen bonding network, reducing the overall intermolecular attraction of water. By reducing the self-association of water, the co-solvent reduces the ability of water to extrude non-polar hydrophobic compounds, thereby increasing solubility. Co-solvents include:

  • Ethanol
  • Propylene glycol
  • Polyethylene glycol 400 (PEG 400)
  • Glycerin
  • Sorbitol and dimethyl sulfoxide
  • Ethanol
  • N,N-dimethyl formamide and N,N-dimethyl acetoamide (DMA)
  • Dimethyl sulfoxide (DMSO)

Why Choose BOC Sciences?

BOC Sciences has a well-equipped, specialized formulation and development (F&D) laboratory. Our team of dedicated scientists is constantly working to improve existing formulations and design new formulations. We can provide you with customized and high-performance formulation design.

References

  1. Chaudhary, A., Nagaich, U., Gulati, N., Sharma, V. K., Khosa, R. L., & Partapur, M. U. (2012). Enhancement of solubilization and bioavailability of poorly soluble drugs by physical and chemical modifications: A recent review. J Adv Pharm Educ Res2(1), 32-67.
  2. Kalepu, S., & Nekkanti, V. (2015). Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharmaceutica Sinica B5(5), 442-453.
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