Pharmaceutical Analysis and Testing

Dosage Form Testing (Examples)

• Tablet testing includes disintegration, friability, hardness, and dissolution testing.
• Cream testing includes rheology testing.
• Tablet testing often employs specific apparatus for disintegration, friability, hardness, and dissolution.
• Creams are often assessed using rheology testing.

Quality of Analysis

• The quality of medicine analysis must meet standards.
• The analysis itself is crucial for ensuring accurate results.
• Ensuring a suitable standard of analysis is vital when assessing medicine quality, even when deviations occur.

Drug Development Stages

• Reformulation is a pre-formulation stage in drug and dosage form development.
• Reformulation precedes formal formulation in drug development.

Quantitative Analysis

• Determines the amounts and proportions of chemical constituents in a substance.
• Quantitative analysis determines the quantities of components in a substance.

Qualitative Analysis

• Identifies the nature of chemical constituents in a substance.
• Qualitative analysis determines the type of components present in a substance.

Analytical Precision

• Accuracy: Closeness of a measurement to the true value.
• Precision: Closeness of multiple measurements to each other.
• Levels of Precision: Includes repeatability, intermediate precision, and reproducibility.
• Analytical methods are characterized by accuracy (closeness to the true value) and precision (consistency of measurements).
• Different aspects of precision exist, such as repeatability (same operator, same instrument), intermediate precision (different operators, same instrument), and reproducibility (different operators/instruments).

Titrimetric and Chemical Analysis

• Principle: A reagent with known concentration reacts with an analyte to determine sample purity.
• Applications: Drug, excipient, and formulation assaying. Specialist applications (e.g., Karl Fischer).
• Advantages: High precision, accuracy, robustness, cost-effectiveness, automatability, no calibration.
• Limitations: Non-selectivity, skilled operator needed. Requires large sample and reagent amounts.
• Titrimetry utilizes a known reagent to find sample purity.

UV-Visible Spectroscopy

• Principle: Compound solution absorbs specific wavelengths (200-700 nm) of radiation. Excited electrons absorb energy, shifting to higher quantum states.
• Applications: Wide use in quantification; determination of pKa, dissolution, solubility, release kinetics, and reaction kinetics.
• Strengths: Easy to use, cost-effective, robust, high precision.
• Limitations: Moderate selectivity. Not applicable for all solutes.
• UV-Vis spectroscopy quantifies substances using light absorption.

IR Spectroscopy

• Principle: EMR (400-4000 cm⁻¹ or 2500-20000 nm) interacts with sample molecules causing bond stretching or bending.
• Applications: Qualitative analysis for excipients, drugs, preliminary compound identification, analysis in complex matrices (creams, tablets), detecting polymorphisms.
• Strengths: Unique fingerprint for compound identification, useful complex matrix analysis.
• Limitations: Rarely quantitative due to sample prep constraints; only useful for detecting gross impurities. Requires technical sample preparation knowledge.
• IR spectroscopy aids in identifying compounds through unique "fingerprints" and can deal with complex samples, but typically is not used for quantification.

Mass Spectrometry

• Principle: Ionisation process creates charged species. Separation based on m/z ratio (mass-to-charge).
• Applications: Drug identification, characterization (molecular weight), impurity characterization (with GC and HPLC), bioanalysis (with GC and HPLC), proteomics.
• Limitations: Expensive equipment, highly skilled operators, less widespread in QC.
• Mass Spectrometry separates ions based on mass-to-charge ratio.

Chromatography

• Principle: Separates mixture components based on partitioning differences between mobile and stationary phases.
• Types: Column, TLC, GC, HPLC.
• Related techniques: Capillary electrophoresis (not a chromatography type).
• Modes: Analytical (lower scale, analysis); Preparative (higher scale, purification).
• Chromatography separates components based on phase partitioning.

High-Performance Liquid Chromatography (HPLC)

• Principle: High-pressure liquid mobile phase flows through a column with stationary phase. Separation based on retention time in the stationary phase. Detection is monitored with a detector (e.g., UV-Vis spectrophotometer).
• Applications: Drug and excipient quantification; stability monitoring; drug/metabolite measurement in biological fluids.
• Strengths: High analytical performance (accuracy, precision, robustness); diverse separation and detection modalities; automatable.
• Limitations: Requires sample preparation; generates organic solvent waste (disposal costs).
• HPLC is a high-performance liquid chromatography method.

Bioanalytical Science

• Application of biological sciences to biological sample study and analysis; a large global industry.
• Bioanalytical science is a significant global industry.

Immunoassay

• Bioanalytical technique using antibody-antigen reaction for qualitative/quantitative analysis of analytes (drugs, biomolecules, metabolites).
• Immunoassay analyzes using antibody-antigen reactions.

Bioanalysis

• Quantitative measurement of drugs, metabolites, biological molecules, and biotics in biological systems.
• Bioanalysis quantifies various components in biological systems.

Pretreatment in Analysis

• Extraction: Removes analyte from sample matrix (formulation, biological fluids) to avoid interference or instrument malfunction due to non-adherence to specifications.
• Importance: Essential for analysis precision and accuracy; various methods (solvent, solid-phase).
• Extraction is often required for sample preparation.

Druglikeness: Lipinski's Rule of Five

• Discusses factors influencing drug properties (e.g., molecular weight).
• Hydrogen bond donors are addressed in the Lipinski's rule, but not elaborated on in detail in this context.
• Lipinski's rule of five considers factors like molecular weight when assessing drug-likeness.

Stability, Impurities, and Residual Solvents

• Stability, impurities, and residual solvents are critical aspects of quality management within drug manufacturing to meet standards.

This quiz covers various aspects of pharmaceutical analysis including dosage form testing, quality of analysis, stages in drug development, and both quantitative and qualitative analysis techniques. Understanding accuracy, precision, and methods such as titrimetry is essential for ensuring the quality of pharmaceuticals.