Pharmaceutical Quality Control Hand Notes

Comprehensive compilation of key topics for pharmaceutical job preparation. Based on original QC note content without alteration.

Clean Room

Definition: A clean room is an engineered space that maintains a very low concentration of airborne particulates. It is well-isolated, well-controlled from contamination, and actively cleaned.

A clean room can be defined as an environment where the supply, distribution, and filtration of clean air are carefully controlled.

Dead Legs:

Sections of potable water piping systems that have been altered, abandoned, or capped so that water cannot flow through them.

Dissolution Process

The dissolution process involves breaking down a substance into smaller molecules to make it soluble or increase its solubility.

  • Testable States: Can be tested on gaseous, liquid, and solid substances.
  • Application: Performed when there is a breakdown of a substance or when particles have low solubility.
  • Purpose: Helps to dissolve substances into soluble forms.
  • Note: Dissolution testing (DT) is a comprehensive concept in pharmaceuticals.

Quality:

The totality of features and characteristics of a product. The ability of a product/service to satisfy stated or implied needs.

Criteria of Quality:

  • Safety
  • Potency
  • Efficacy
  • Stability
  • Acceptability
  • Regulatory Compliance

Quality Assurance (QA):

Operational techniques and activities used to fulfill requirements for quality. QA = Testing + Assessment.

Sample:

A portion of a material collected according to a defined sampling procedure.

Sampling:

The process of taking a small portion from a lot/batch for test and analysis.

Sampling Plans

n-plan: Used when the material to be sampled is considered uniform and is from a recognized source.

Formula: √n + 1

p-plan: Used when the material is confirmed and received from a recognized source. Purpose is to test for identified parameters.

Formula: P = 0.4√N (where N is the number of sampling units)

r-plan: Used when material is suspected to be non-uniform and received from a not well-known source.

Formula: n = 1.5√N

HPLC (High Performance Liquid Chromatography)

Principle: HPLC is an analytical chemistry technique used to separate, identify, and quantify components in a mixture.

It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with solid adsorbent material.

Each component interacts differently with the adsorbent material, causing different flow rates and separation.

Parts of HPLC:

  • Pump
  • Column
  • Detector
  • Auto-injector
  • Oven

IR & FTIR Spectroscopy

Infrared Spectroscopy (IR): Deals with the infrared region of the electromagnetic spectrum (light with longer wavelength and lower frequency than visible light).

FTIR (Fourier Transform Infrared): A measurement technique that allows recording of infrared spectra.


Total Organic Carbon (TOC):

Refers to the amount of organic carbon in a biological formation. In petroleum geology, 2% is a rough minimum for source rock.

Karl Fischer Titration

Determines water content in a sample based on an iodine/iodide redox reaction.

It is a titration method where reagent is added until all water is consumed (endpoint reached).

Reaction Steps:

Step 1: SO₂ + MeOH + B → MeSO₃⁻ + HBr⁺
Step 2: MeSO₃⁻ + H₂O + I₂ + B → MeSO₄⁻ + HBr⁺ + I⁻

Weight Variation of Tablets:

Standard Weight Range Allowed % Difference
BP (British Pharmacopoeia) ≤ 80 mg 10%
80 to 250 mg 9.5%
> 250 mg 5%
USP (United States Pharmacopeia) ≤ 130 mg 10%
130 to 324 mg 9.5%
> 324 mg 5%

Moisture Content:

Measurement of moisture in a wet solid collected on a dry weight basis.

Me = (Weight of water in sample / Weight of dry sample) × 100

Loss on Drying (LOD):

Moisture in a solid can be expressed on a wet-weight basis.

LOD = (Weight of water in sample / Total weight of wet sample) × 100

Calibration:

Demonstration that a measuring device produces results within specified limits by comparison with a reference standard device.

Melting Point:

The temperature at which a substance changes state from solid to liquid at atmospheric pressure.

OOT (Out of Trend):

An examination, measurement, or test result that does not comply with pre-established criteria.

A result that does not follow the expected trend compared with other batches or previous results during a stability study.

Document:

A written, drawn, presented, or recorded presentation of thoughts.

Record:

Historical files that provide proof of existence and evidence of activities performed.

Normalization:

Gram equivalent weight of solute per liter of solution.

Reference Standard:

Any material of known identity, purity, or potency used as a benchmark for comparison.

Important Abbreviations:

  • COD: Chemical Oxygen Demand
  • LOD: Loss on Drying
  • OOT: Out of Trend
  • COS: Condition of Specification
  • QA: Quality Assurance
  • QC: Quality Control