Quality Control in Pharmaceutical Manufacturing

Quality Control in Pharmaceutical Manufacturing: Solid Dosage Forms

• Quality control (QC) is crucial in pharmaceutical manufacturing. It ensures the safety, efficacy, and consistency of medicinal products.
• This presentation focuses on QC procedures for solid dosage forms, specifically tablets.
• Tablets are a prevalent dosage form in the pharmaceutical industry.

Understanding Quality Control in Pharmaceutical Manufacturing

• Quality Assurance (QA) aims to prevent product defects. It creates a system for ensuring quality throughout the manufacturing process.
• QC is part of QA, focusing on the direct testing and monitoring of products.
• QC ensures that manufactured products meet predefined standards. It involves sampling, testing, documentation, and analysis to identify deviations.

Solid Dosage Forms

• Tablets: Made by compressing a mix of active pharmaceutical ingredients (APIs) and excipients. They come in various forms (buccal, sublingual, chewable, enteric-coated, effervescent).
• Capsules: Enclose APIs and excipients in a shell (either powder or granule form). Two types: hard-shelled (contains powder) and soft-shelled (contains oil).
• Granules: Dry preparations with a definite particle size, made from APIs and suitable excipients.
• Lozenges: Hard medicines that dissolve slowly in the mouth, prolonging the effects of the medicine at the site of action (e.g., antiseptic, antitussive).
• Suppositories: Solid dosage forms applied to the rectum. Composed of an active ingredient in a suppository base.

Quality Control of Tablets: A Comprehensive Approach

• Weight Uniformity: Ensures each tablet contains the correct dosage of active ingredient, ensuring consistent therapeutic efficacy.
• Content Uniformity: Determines the accuracy of active ingredient content in individual tablets, ensuring consistent dosage.
• Dissolution: Evaluates how readily the active ingredient dissolves from the tablet, impacting bioavailability and effectiveness in the body.
• Mechanical Strength: Measures the tablet's hardness and resistance to breakage during handling and manufacturing.

Weight Uniformity Test: Ensuring Consistent Dosage

• Sampling: Randomly select 20 tablets from the batch.
• Individual Weighing: Weigh each tablet accurately.
• Deviation Calculation: Calculate percentage deviation from the average weight.
• Acceptance Criteria: Compare deviations to established standards to ensure compliance.

Weight Uniformity Test: Aspacid 75 mg

• Sampling: Randomly select 20 tablets from the production run.
• Calculate individual and average weighing: Sum of the weights divided by 20.
• Deviation calculation: ((Individual weight-Average Weight) / Average Weight)*100

Acceptance Criteria

• Tablets weighing 80 mg or less, deviations should not exceed ±10%.
• Tablets between 80-250 mg, deviations should not exceed ±7.5%.
• Tablets over 250 mg, deviations should not exceed ±5%.
• The test is considered passed if not more than two tablets deviate beyond the acceptable limit, and none exceeds double the limit.

Causes for Weight Variations

• Size and distribution of granules (being compressed).
• Poor flow and high-speed turret speed (incomplete filling).
• Poor mixing (uneven distribution of lubricants and glidants).
• Variability in lower punch length (inconsistent fill).

Content Uniformity Test: Method

• Sampling: Randomly select 30 tablets from batch (for tablets less than or equal to 40 mg).
• Initial Assay: Determine the average content of active ingredient in 10 tablets by analysis.
• Acceptance Criteria: Individual tablet content must fall within ± 15% for content less than or equal to 40 mg and between 75% to 125% range for any individual to comply with the test.
• Further Assay: Assay the remaining 20 tablets for a full batch uniformity analysis.

Dissolution Test: Evaluating Active Ingredient Release

• Purpose: Assesses how rapidly the active ingredient dissolves.
• Methodology: Immersing tablets in a simulated fluid at controlled temperatures and stirring speeds.
• Acceptance Criteria: Ensures the active ingredient dissolves within specified timeframes and extent.

Mechanical Strength: Ensuring Tablet Integrity

• Hardness Test: Evaluates tablet resistance to crushing and breakage.
• Friability Test: Measures tablet's resistance to abrasion during handling and transport.

Visual Inspection: Ensuring Tablet Appearance and Uniformity

• Appearance: Checks for discoloration, defects, or inconsistencies.
• Shape: Verifies consistency with specifications, free from distortions.
• Size and Dimensions: Measures diameter and thickness using instruments (e.g., vernier calipers) to check uniformity within the batch.

In-Process Control: Maintaining Quality Throughout Production

• Continuous monitoring and adjustment of critical parameters during manufacturing.
• Helps minimize manufacturing deviations and ensure product consistency.

Essential Instruments for Quality Control

• Analytical Balances: Precision measurement of weights.
• Dissolution Apparatus: Testing how quickly the active ingredients dissolve.
• Disintegration Tester: Assessment of whether the tablet breaks into smaller particles.
• Hardness Tester: Measures the hardness of the tablets.
• Friability Tester: Measures the resistance of the tablets to abrasion.
• Vernier Caliper or Micrometer: Measuring tablets' dimensions for uniformity.
• UV-Vis Spectrophotometer: Instrumental analysis of the active ingredient or other components being assessed.