Drug-Excipient Compatibility Studies

Study of drug-excipient compatibility is an important phase in the pre-formulation stage of drug development. The potential interactions between drugs and excipients have effects on the chemical, physical, bioavailability and stability of the dosage form. Creative Biolabs provides drug-excipient compatibility studies to provide data for drug-excipient interaction which can further help in selection of excipient for the development of stable dosage form.

Excipients are substances which are included along with the active pharmaceutical ingredient (API) in dosage forms. Most excipients have no direct pharmacological action but are important for facilitating the administration, modulating the release of the active component and stabilizing API against degradation. However, inappropriate excipients can also give rise to inadvertent and/or unintended effects which can affect the chemical nature, the stability and the bioavailability of the API, and consequently, their therapeutic efficacy and safety. Studies of drug-excipient compatibility represent an important phase in identifying interactions between potential formulation excipients and the API in the development stage of all dosage forms.

Creative Biolabs provides drug-excipient compatibility studies which focus on three types of incompatibility:

• Physical incompatibility: We assess the change in the physical form of the formulation, like color changes, dissolution, solubility, sedimentation rate, liquefaction, phase separation or immiscibility.
• Chemical incompatibility: We assess undesirable react between API and excipients to monitor if compounds undergo hydrolysis, oxidation, reduction, precipitation, decarboxylation, and racemization.
• Therapeutic incompatibility: We assess the interactions which are observed after administration of the medication. Examples of biopharmaceutical interactions are premature breakdown of enteric coat, interactions due to adjunct therapy and increase in gastrointestinal motility.

Analytical Techniques Used to Detect Drug-Excipient Compatibility

Creative Biolabs uses different thermal and non-thermal analysis methods, tools and software for incompatibility tests. Analytical tools for compatibility assessment of APIs include:

Thermal methods of analyses

Thermal analysis plays a critical role in compatibility studies and has frequently been employed for quick assessment of physicochemical incompatibility. We provide three different types of thermal analyses, which include:

• Differential scanning calorimetry (DSC)

DSC curves of pure components are compared to the curves obtained from 1:1 physical mixtures. A significant shift in the melting of the components or appearance of a new exo/endothermic peak and/or variation in the corresponding enthalpies of reaction in the physical mixture indicate incompatibility.

• Isothermal microcalorimetry

It allows determination of minute amounts of evolved or absorbed heat. The thermal activity of API, excipient and their mixtures are measured individually in the calorimeter and the thermal activity (heat flow) at a constant temperature is monitored.

• Hot stage microscopy (HSM)

HSM is a visual thermal analysis technique, which allows efficient monitoring of solid state interactions that could be erroneously interpreted as incompatibility by DSC. This technique only requires very small quantity of sample when performing compatibility studies.

Spectroscopic techniques

• Vibrational spectroscopy
  • FT-IR Spectroscopy
  • Diffuse Reflectance Spectroscopy (DRS)
• Powder X-ray diffraction (PXRD)

  PXRD is of great help for compatibility studies during processes like compression, wet granulation, etc. and bring on changes in crystallinity/amorphicity and polymorphic forms of API in the presence of excipients.

• Solid state nuclear magnetic resonance spectroscopy (ss NMR)

  ss NMR has shown immense potential in the qualitative and quantitative analysis of pharmaceutical solids. It has a unique advantage for detecting compatibility in crystalline as well as amorphous components in a mixture.

Microscopic technique

• Scanning electron microscopy (SEM)

Chromatography

• Self-Interactive Chromatography (SIC)
• Thin Layer Chromatography (TLC)
• High-Performance Liquid Chromatography (HPLC)

HPLC exhibit a percentage loss of the API. We provide liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS) to further characterize the incompatibility products.

For more detailed information, please feel free to contact us or directly sent us an inquiry.

References

1. Patel P, Ahir K, Patel V, et al. (2015). “Drug-Excipient compatibility studies: First step for dosage form development”. The Pharma Innovation Journal 4(5): 14-20
2. Dinte E, Bodoki E, Leucuta S et al. (2013) “Compatibility Studies Between Drugs and Excipients in the Preformulation Phase of Buccal Mucoadhesive Systems” Farmacia 61(4): 703-712

For Research Use Only.