Applications in Pharmaceuticals

Pharmaceuticals are drugs and medications that are discovered and developed to be used in the diagnosis, treatment, or prevention of disease and for restoring, correcting, or modifying organic functions. Sri Lanka’s pharmaceutical market is estimated to be worth USD $ 400 million per year. In order to produce safe and efficacious pharmaceuticals, we perform several analyses such as the chemical and physical characterization of APIs and excipients, qualitative analysis of APIs and stability testing of pharmaceutical drug products. Some pharmaceutical applications that are possible to be carried out at the SLINTEC premises using the equipment available for analysis are given below.

Transmission Electron Microscopy (TEM)

• Identification of amorphous or crystalline phases present at low concentration
• Identification of different polymorphs
• Characterization of nanosized API crystals
• Detection of trace impurities in pharmaceuticals and analyse them by EDS

Scanning Electron Microscopy (SEM)

• Use of EDS maps and BSE (back scattering electron) images of tablet cross section for the direct examination of excipient and active pharmaceutical ingredient distribution
• Identification and characterization of impurities/ foreign particulate matter, degradation products present in pharmaceutical products
• Measure the thickness of tablet coatings
• Investigate microstructure, surface topography, shape, size and morphology of a range of organic and inorganic pharmaceutical ingredients
• Use in process quality control to make sure each batch of excipients or APIs are consistent and to verify the presence of the ingredients as individual particles or as aggregates

Atomic Force Microscopy (AFM)

• Characterizing the morphology and roughness of granules to correlate their surface structure to the underlying physiochemical and mechanical processes during the manufacturing process
• Evaluate surface morphology, pore structure and roughness of the coatings of the tablets
• Study of crystal growth process to optimize the growth condition in producing a desired morphology 

Optical Microscopy

• Microscopic analysis of pharmaceutical materials to optimize particle size, morphology and roughness during production
• Rapid discrimination between amorphous and crystalline materials
• Identification of contaminants

Thermogravimetric Analysis (TGA)

• Determination of the amount of weight change of a pharmaceutical ingredient, either as a function of controlled temperature, or isothermally as a function of time, in an atmosphere of high purity nitrogen or compressed air
• Determination of decomposition, vaporization or sublimation temperatures of pharmaceutical ingredients

Differential Scanning Calorimetry (DSC)

• Identification of polymorphic formation under various heating and cooling conditions (condition needed to induce polymorph formation)
• To monitor samples for the development of polymorph under various storage conditions or under various manufacturing conditions such as grinding, heating, mixing and drying
• Detection of purity (sharp melting endotherm indicates the relative purity whereas a broad asymmetric curve suggests impurity)
• The detection of drug excipient incompatibility/interactions
• Study of complexes and inclusion compounds (to find how complexation and inclusion affect the drug activity
• Determination of the thermal transitions such as melting point, recrystallization and glass transition  

Dynamic Mechanical Analysis (DMA)

• Determination of the glass transition temperature and modulus of packaging materials

Fourier Transform Infrared Spectroscopy (FTIR)

• Identification of functional groups of active pharmaceutical ingredients, excipients and packaging materials
• Detection of impurities
• Determination of molecular structure (along with other spectroscopic techniques such as NMR)
• Identification of raw materials by comparing the spectra obtained from the raw materials and the reference materials 

Raman spectroscopy

• Analyze subtle structural changes such as polymorphism and crystallinity of pharmaceutical ingredients
• Identification of raw materials by comparing the spectra obtained from the particular materials and its reference material
• Differentiation of counterfeit drugs from originals
• Analyze/detection of degradation products of pharmaceuticals during storage in order to maximize product shelf life

UV/Visible Spectroscopy

• Quantitative analysis of active pharmaceutical ingredients in formulation where there is no interference from excipients
• To determine the release of drugs from formulation with time
• Detection of impurities in organic molecules
• Detect the presence or absence of a functional group in a compound

Fluorescenece Spectroscopy

• Detection and quantification of organic compounds that show native fluorescence

X-Ray Powder Diffraction (XRD)

• Identification and characterization of polymorphs of drug substances and monitoring their stability
• Screening the crystal structure and lattice parameter of pharmaceutical ingredients
• Use as a tool for systematic drug excipient compatibility studies in preformation
• Monitoring batch/dosage uniformity
• Monitoring the crystal morphology of active pharmaceutical ingredients or the excipients in order to investigate changes in morphology of excipients or in the crystalline state of active ingredients in the final product as a result of the manufacturing process

Nuclear Magnetic Resonance Spectroscopy (NMR)

• Identification of drug substances and impurities arising from the synthesis pathway and degradation of residual solvents
• Identification and characterization of polymorphs using solid state NMR
• Elucidation of molecular structure by a combination of both 1D and 2D NMR spectroscopic experiments

Inductively Coupled Plasma- Mass Spectrometry (ICP-MS)

• Quantification of elemental impurities present in pharmaceuticals and their ingredients

Atomic Absorption Spectroscopy (AAS)

• Quantification of elemental impurities present in pharmaceuticals and their ingredients

X-Ray Fluorescence Spectroscopy (XRF)

• Tablet imaging to examine excipient and active pharmaceutical ingredient distribution and mixing uniformity
• Identification of contaminant in pharmaceutical ingredients and products

CHNS Analysis

• Determination of carbon, hydrogen, nitrogen and sulfur content in pharmaceutical ingredients

Energy Dispersive X-Ray Spectroscopy (EDX)

• Use of EDS maps of tablet cross section for the direct examination of excipients and active pharmaceutical ingredient distribution within a tablet

Particle Size Analysis

• Particle size distribution analysis of active pharmaceutical ingredients and excipients

XPS

• Analyze the surface chemistry of pharmaceuticals