PMCY 4500L - Exam 2

Define “thermogravimetric analysis”

a technique in which the mass of a substance is monitored as function of temperature or time as the sample specimen is subjected to a controlled temperature program in a controlled atmosphere

measures a sample’s weight as it is heated or cooled in a furnace

What gases provide the controlled atmosphere in TGA?

• air

• N2

• CO2

• He

• Ar

How is the weight change against temperature during TGA plotted? (what is the name)

thermogram OR thermogravimetric curve

What are the major components of TGA instrumentation?

• furnace

• furnace controlled thermo-balance

• recorder

Who are the major manufacturers of TGA instrumentation?

• Perkin Elmer

• Shimadzu

• Hitachi

What are the main applications of TGA? (what is it used for)

• determination of moisture & volatile content

• degradation temperature

• ash/residue value

(T/F) TGA only observes weight loss.

False — it observes weight change overall, including loss and gain

How can weight loss occur in TGA?

• decomposition — breakdown of chemical bonds

• evaporation — loss of volatiles and moisture

• reduction — sample interactions with a reducing environment (atmospheric hydrogen)

Define “decomposition”

breakdown of chemical bonds

Define “evaporation”

loss of volatiles and moisture

Define “reduction”

sample interactions with a reducing environment (atmospheric hydrogen)

How can weight gain occur in TGA?

oxidation — sample interactions with an oxidizing environment (atmospheric oxygen)

Define “oxidation”

sample interactions with an oxidizing environment (atmospheric oxygen)

What are the categories of factors that affect thermograms?

• instrumental factors

• sample characteristics

What types of instrumental factors can affect thermograms?

• furnace heating rate

  • temperature at which a compound decomposes depends directly upon the heating rate

  • generally a lower heating rate (around 5C per minute) provides a higher resolution

• furnace atmosphere

  • furnace atmosphere has profound effects on the decomposition behavior of a sample

  • pure nitrogen is commonly used for an inert environment

What gas is used to create an inert environment in TGA?

pure nitrogen (N2)

What types of sample characteristics can affect thermograms?

• weight of the sample

  • smaller sample yields better resolution as it eliminates temperature gradients within the sample

• sample particle size

  • smaller particle size with a uniform distribution is recommended for minimal temperature fluctuations

What instrument did we use for the TGA lab?

Perkin Elmer TGA 4000

What is the USP chapter for the TGA lab? (name and number)

<891> Thermal analysis

Is TGA a good method to determine the various hydrate forms of an ingredient?

TGA is a very effective and widely used method for characterizing different hydrate forms of an ingredient, especially when combined with other techniques for confirmation. It provides both qualitative and quantitative data on how much water is present and the temperatures at which it is released, making it a strong analytical tool for studying hydrates.

Is TGA analysis a good analytical method for water determination versus “Loss on Drying” or “Karl Fischer Titration?”

If water determination is the primary goal and high specificity is required, Karl Fischer Titration is the best choice. TGA and LOD can provide useful estimates, but they are less specific, and the results may include other volatile components along with water.

• TGA: Useful for multi-purpose analysis (e.g., thermal decomposition and moisture), but less specific for water determination. It is good for solid samples where moisture and other thermal behaviors are of interest, but not ideal when precise water measurement is required.

• LOD: Simple, widely used for approximate moisture content, but also not specific for water since it measures total volatile loss.

• Karl Fischer Titration: The gold standard for precise water determination, especially when accuracy and specificity are required. It’s ideal for pharmaceuticals, oils, plastics, and other materials where knowing the exact water content is critical.

What was the topic of the student presentation? (Jasmine, Isabella, Abby, and Emma)

21 CFR 210 — Current Good Manufacturing Practices (cGMP) in Manufacturing Processing, Packing, or Holding of Drugs (general)

What is the Code of Federal Regulations?

The codification of the general and permanent rules published in the Federal Registrar by the departments and agencies of the Federal Government

What are the subparts of 21 CFR 210?

• 210.1 — status of current good manufacturing practice regulations

• 210.2 — applicability of current good manufacturing practice regulations

• 210.3 — definitions

Why is the status of cGMP regulations regulated? (purpose of regulation)

• to establish baseline standards for ensuring drug safety, quality, and effectiveness

• To confirm the drug has the correct identity, strength, quality, and purity

Who needs to follow cGMP regulation standards?

• Methods used in manufacturing, processing, packing, or holding of a drug for both domestic and foreign firms supplying drugs for U.S. distribution

• Facilities or controls used in these processes

What types of products/materials does 21 CFR 210 cover?

• finished pharmaceuticals

• bulk drug substances

• components of drugs for human and veterinary use

(T/F) If a person engages in only certain operations subject to regulations in one part but not in another, they need to comply only with the regulations relevant to their specific operation.

True

What are the consequences of not complying with cGMP regulations?

• the drug is considered “adulterated”

• both the drug and the responsible person/manufacturer will face regulatory action

Define “adulterated”

Containing impurities or harmful substances, often due to improper handling or contamination during production, which can compromise safety, efficacy, or quality of a product

What other parts of the CFR Title 21 supplement Part 210?

• 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals)

• 225 (Current Good Manufacturing Practice for Medicated Feeds)

  • animal drugs

• 226 (Current Good Manufacturing Practice for Type A Medicated Articles)

  • animal drugs

• 600-680 (biological products)

• 1271 (human cell/tissue-based products)

What types of drugs are exempt from 21 CFR 211 regulations, and what else are they expected to follow?

Investigational drugs for phase 1 studies

subject to 21 U.S.C. 351 (a)(2)(B)

What is 21 U.S.C. 351 (a)(2)(B)?

refers to a drug that must be manufactured, processed, packed, or held using methods, facilities, and controls that conform to cGMP. It also needs to meet safety requirements, and has correct identity, strength, quality, and purity

(T/F) If an investigational drug for phase 1 studies does not meet cGMP standards, they are still able to satisfy 21 U.S.C. 351 (a)(2)(B), it just may be a different way.

False — Non-conformity with cGMP results in the drug not meeting these standards.

When are investigational drugs not exempt from 21 CFR 211 regulations?

once the drug is used in phase 2 or 3 studies or if it has been lawfully marketed.

In such cases, compliance with part 211 is required for the phase 1 study drug

Define “active ingredient”

any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation

Define “inactive ingredient”

any component other than an active ingredient

Define “batch/lot”

a specific quantity of a drug or other material that is intended
to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture

Define “lot/batch number”

any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacture, processing, packaging, holding and distribution of a batch or lot of drug product or other material can be determined

What does GLP stand for?

Good Laboratory Practices

What does GCP stand for?

Good Clinical Practices

What does GMP stand for?

Good Manufacturing Practices

What are the different types of GXPs documentation?

• GLP — good laboratory practices

• GCP — good clinical practices

• GMP — good manufacturing practices

• regulatory compliance

• Enforcement Code of Federal Regulations

What does SOP stand for?

Standard Operating Procedure

What is a Standard Operating Procedure?

• step-by-step how-to instructions

• instructional resource without asking for directions

What is the importance of SOPs?

being able to perform the task in a consistent manner

What does MBR stand for?

manufacturing batch record

What is a manufacturing batch record?

a complete product history, including the raw materials and equipment used, procedures followed, and quality records

What is the importance of a MBR?

a high-quality batch record is crucial for verifying the quality of the pharmaceutical product

(T/F) Manufacturing batch records are only available as hard-copy templates that are written in.

False — online/electronic batch records are available too

(T/F) Every patient deserves drugs that are safe and efficacious.

True

What is the key value for any manufacturer of (bio)pharmaceuticals?

quality

Describe a typical manufacturing workflow and release

1. master batch formula is created and finalized

2. using MBF, manufacturing batch record is made

3. batch number is issued and manufactured

4. sampling is performed by quality inspectors

5. quality control laboratory (QC)

6. quality assurance (QA)

7. certificate of analysis and batch release

8. product is marketed and money is made

Define “batch number”

unique identifier that is crucial for tracking, quality control, and ensuring traceability in pharmaceutical drug development. It helps in monitoring the production process and managing recalls if necessary.

What is the difference between quality control and quality assurance?

quality assurance: focuses on processes and systems to prevent defects and ensure standards are met throughout production; ensures quality requirements are fulfilled; PROACTIVE

quality control: emphasizes inspection and testing of final products to identify and rectify defects after production; ensures medications are safe and effective; REACTIVE

What type of tests do quality control scientists do?

analytical tests and specifications

What type of tests do quality assurance scientists do?

review batch manufacture process and analytical data

Who performs the sampling in a typical manufacturing workflow and release?

quality inspectors

(T/F) Drug substance and API are two different things.

False — they are the same

Define “drug product/dosage form”

combination of API and excipients to facilitate dosing, administration, and delivery of a medicine to the patient

List examples of dosage forms (general)

• oral

• injection

• topical

• inhalation

List examples of oral dosage forms

• SOLIDS

  • tablets

  • capsules

  • granules

  • powders

• LIQUIDS

  • solutions

  • suspensions

  • emulsions

What are the different possible functions of excipients?

• diluents/fillers

• binders

• disintegrants

• lubricants

• glidants

• surfactants/wetting agents

Define “pharmaceutical excipients”

inert substance that helps form a vehicle for the API

additives used to convert API into actual dosage forms

What does the combination of an API and excipients facilitate?

• dosing

• administration

• delivery

What is the function of filler/diluent excipients?

provide bulk & impart powder characteristics

What is the function of binder excipients?

bind and hold the drug product together —> aid in granulation of fine powders for tablets

What is the function of disintegrant excipients?

promotes capsule plug or tablet disintegration into smaller fragments

What is the function of lubricant excipients?

reduce friction and help tablet ejection from manufacturing lab (so it doesn’t stick to the mold during compression)

What is the function of glidant excipients?

increase powder flow properties (helps it go through the equipment pipes)

What is the function of surfactant/wetting agent excipients?

improve wettability/solubility of API

What are examples of filler/diluent excipients?

• microcrystalline cellulose

• lactose

• starch

• CaPO4

What are examples of binder excipients?

• Hypromellose

• povidone

• starch

• natural gums

• maltodextrins

What are examples of disintegrant excipients?

• sodium starch glycolate

• croscamellose sodium

• crospovidone

What are examples of lubricant excipients?

• magnesium stearate

• talc

• stearic acid

• sodium stearyl fumarate

• calcium stearate

What are examples of glidant excipients?

• (fumed) silica

• talc

What are examples of surfactant/wetting agent excipients?

• sodium lauryl sulfate

• tweens

• poloxamers

What type of excipient is microcrystalline cellulose?

filler/diluent

What type of excipient is lactose?

diluent/filler

What type of excipient is starch?

diluent/filler & binder (multi-functional)

What type of excipient are sugars?

diluent/filler

What type of excipient is dicalcium phosphate?

diluent/filler

What type of excipient is hypromellose?

binder

What type of excipient is povidone?

binder

What type of excipient are natural gums?

binder

What type of excipient are maltodextrins?

binder

What type of excipient is sodium starch glycolate?

disintegrant

What type of excipient is croscamellose sodium?

disintegrant

What type of excipient is crospovidone?

disintegrant

What type of excipient is magnesium stearate?

lubricant

What type of excipient is talc?

lubricant & glidant

What type of excipient is stearic acid?

lubricant

What type of excipient is sodium stearyl fumarate?

lubricant

What type of excipient is calcium stearate?

lubricant

What type of excipient is (fumed) silica?

glidant

What type of excipient is sodium lauryl sulfate?

surfactant/wetting agent

What type of excipient are tweens?

surfactant/wetting agent

What type of excipient are poloxamers?

surfactants/wetting agents

What is the BCS classification of piroxicam?

Class II

Define “biopharmaceutical classification system”

A framework that classifies pharmaceutical compounds into four categories based on their permeation and solubility characteristics

helps predict the oral bioavailability of drugs and guides formulation development and regulatory assessments