Pharmaceutical Analysis: Methods and Quality Control

Posted on Nov 16, 2024 in Chemistry

Milk of Magnesia (Magnesium Hydroxide)

This alkalinization is based on a neutralization between milk of magnesia, which is magnesium hydroxide, and auxiliary substances such as stabilizers, preservatives, and viscosity agents like carboxyl methyl cellulose.

Used as an indicator (heliantina 3.1 to 4.4)
Reference value: 7.5 – 8.5 g% Mg(OH)2

Saline Analysis (Argentometric)

The Volhard method for residual valuation is commonly used and involves two determinations:

Direct determination: Silver salts
Residual determination: Halides, sodium chloride

HNO3 avoids interference in the precipitate (AgCl, carbonates, oxalates) and with iron in the indicator. It prevents interference and reduces silver salts.

Nitric acid does not react as it is not involved in the reactions.

Ferric alum as indicator
Reference value: 0.86 to 0.94 g% NaCl

Permanganometric Method

This method uses the oxidizing power of potassium permanganate in a strongly acidic medium, which decomposes and releases nascent oxygen.

Benefits: Fast, relatively economical

Disadvantages: Stabilizers and preservatives in hydrogen peroxide can interact with KMnO4 if the assessment is not done with a continuous drip, risking absorption of stabilizers by KMnO4.

Hydrogen Peroxide
Reference value: 2.6 – 3.4 g% H2O2

Iodometry

This method is based on the reducing action of potassium iodide (KI) in a strongly acidic medium with hydrogen peroxide, which acts as an oxidizing agent.

Iodometrically, the maturity rate of B-lactam antibacterials is investigated through the oxidizing power of iodine. This method can be used for the entire penicillin group.

Basis: In alkaline hydrolysis of the B-lactam ring, all B-lactam rings have sulfur and nitrogen in common.

The B-lactam ring reacts with a strong base, and hydrolysis forms the penicillanic acid (NCOH).

Amoxicillin chemical name: alpha, paramicrobecinpenicillin.

Reference value: 97.5 – 98.5 g%

Historical Context of Pharmaceutical Regulation

Nuremberg 1559: Improved pharmaceutical regulation and a standardized system for weighing drugs.

Valerius Cordus: First official pharmacopoeia, Dispensatorium.

Identify: Recognize if a substance is assumed or searched.
Characterize: Determine peculiar attributes of a substance.
Recognize: Examine a substance carefully to establish its identity and nature.
Confirm: Reach final certainty.
Differentiate: Distinguish a substance from others that are very similar.

Resource ID: Organoleptic characterization, testing orientation, physical constants, systematic analytical marches, organic compounds analysis (elemental analysis, functional analysis), solubility analysis.

Sampling

Sample unit meets q: Shows characteristics of the lot.
Increase: A given quantity (q) is taken from the sample unit.
Main sample: Sample (q) is obtained from the increased mixture.
Subsample (q): Result of subdividing the main sample.
Analytical sample (q): Sample subjected to quality control.

Types of lots:

  • Homogeneous: Composition does not vary over time.
  • Heterogeneous:
  • Discrete or discontinuous changes (tablets, suspension).
  • Continuous changes (fluids, granular).

100% inspection lot: Limited time, cost, and personnel.

Batch sampling, sample unit increase, sample reduction (main sample, subsample), sample preparation (analytical sample).

Purpose: Obtain a representative and adequate sample.

Quality of sampling procedure: Material properties (physical nature, homogeneity), analytical process properties (size and stability of the sample).

Applications of sampling procedure: Lots of raw materials (MP), intermediate phase lots (Mx), finished product batches, material description.

Sampling stages: Random sampling, bulk lots, lots per unit. For lots greater than 100, sample no less than 10.

Random sampling methods: Urn method, random number table method.

Systematic sampling: Sampling at regular intervals (d).

Reducing solid samples: Quartering method, conification.

Samples sent to the laboratory: Reserve analysis, against expert opinion.

Adulteration

Adulteration is intentional fraud or deceit committed with malice to increase or maintain commercial profit margins.

Responsibility of the pharmaceutical analyst: Strictly monitor the quality of drugs and medicines.

Signs of adulteration: Nature and physical appearance, unusually low price, mechanical difficulties, supplier reputation.

Common adulteration techniques: Substitution, addition or dilution, subtraction, omission, diminution, dissimulation, imitation, use of prohibited drugs, bad or fake medication, altered labeling.

Drug Alteration

Alteration is a natural cause that results in injury, damage, or contamination of a drug, affecting its appearance, quality, presentation, or composition.

Concurrent conditions: Sensitivity or lability, presence of natural agents, occurrence of other factors, technological errors, complex formulas, storage conditions.

Reaction orders:

  • Zeroth-order reaction: Rate is independent of initial concentration.
  • First-order reaction: Rate is directly proportional to initial concentration.
  • Second-order reaction: Rate is proportional to the concentrations or their second power.
  • Pseudo-first-order reaction: Rate does not depend on the concentration of reactants.

Agents of alteration:

  • Physical: Infrared, gravitational energy, interfacial, mechanical, electrical, sound.
  • Chemical: Atmospheric air, auxiliary ingredients, primary packaging, enzymes.
  • Biological: Bacteria, yeasts, and molds.

Degradative phenomena: Racemization, complexation, enzymatic digestion, sorption, desorption, dextran fermentation, putrefaction, mold formation.

Methods to study stability: Classical method, accelerated method, molecular reaction, reaction order, reaction rate.

Degradative phenomena:

  • Physical: Evaporation, fusion, concentration, deliquescence, cremation, flocculation.
  • Chemical: Peroxidation-rancidity (acid, peroxide, aldehyde, ketone), reduction (turbidity, discoloration, crystallization, precipitation).

Quality Control Analytical Protocol Logging

Final evaluation of the drug, bibliographic authority, analyst’s signature, head of department’s signature.

Bioavailability

Bioavailability is the experimental study of the drug absorption process, including lipid solubility, molecular size, affinity for the specific site, and particle loading.

Polymorphisms

Polymorphisms involve studying the different physical properties acquired by many glazed drugs according to the preparation method (barbiturates, sex hormones, some bacterial).

Annual File

An annual file is useful for scheduling sample withdrawal in an agile and efficient way. The file should include product information, storage conditions, date of sample removal, and type of requested ratings.