Unit 4 Flashcards
What are the benefits of using solid dosage forms?
- Dose accuracy
- Stability of the drug
- Portabilty
- Uniformity of dose
- Reproducibilty
- High mechanical strength
- Tamper resistance
- Masking of taste, odour
- Easy to pack, handling and transportation
What are the disadvantages of using solid dosage forms?
- Not suitable for unconscious patients.
- May be difficult to swallow (dysphasia)
- Formulation complications
- Not preferable for acid labile and stomach irritant drugs.
What are the benefits of using liquid dosage forms?
- Easy to swallow
- Easy to manufacture
- Fast absorption
- Improves bioavailability
- Less processing steps
- Less excipients required as compared to tablets.
What are the limitations of using liquid dosage forms?
- Non uniformity of dose
- Prone to microbial attack
- Bulky
- More chance of loss by the breakage during shipping & transportation.
- Unsuitable for unpleasant taste & obnoxious odour drugs.
- Less stability.
What are the benefits of using semisolid dosage forms?
- Easy to use
- More stable than liquid dosage form.
- Avoids first pass metabolism.
- Local action of drug on affected area.
- Patient convenience (easy to apply and remove).
What are the limitations of using semisolid dosage forms?
- Difficult to handle.
- Chances of contamination (application with finger).
- More prone for environment to get affected.
- May cause staining & irritation.
What are the benefits of using gaseous dosage forms?
- Easy to handle & convenient.
- Withdrawal of dose without contamination.
- Environmental of unstable drug.
- Provides medication to local areas.
- Dose adjustments possible
- Tamper proof
What are the limitations of using gaseous dosage forms?
- Expensive
- May create environmental hazards
- Dosing is not reproducible
- Not reliable performance
- Limited safety.
Why are drug substances often combined with additives?
To ensure precise dosing and to achieve the desired therapeutic effect.
What is the importance of selection of excipients in drug formulation?
Excipients can alter the therapeutic properties of the drug.
What is a common solution for handling low-dose medications?
Preparing dosage forms such as tablets or capsules with bulking agents (diluents).
What are the benefits of controlled /extended release dosage forms?
They allow reduced frequency of administration without sacrificing efficiency.
What are the overall aim of dosage form design?
To increase stability of drug substances, extend shelf life, ensure accurate dosing, and deliver drugs in a suitable form.
What are the stages of involved in the development of dosage forms?
1) Preformulation
2) Drug product formulation development.
3) Manufacturing
What are biological properties of a drug?
This relates to its ability to get to a site of action and elicit a biological response.
What is the solubility of a drug classified as and what is its significance?
This is classified in terms of the solvent required to solubilise 1g of the drug at a specified temperature, which is determined by the kinetic solubility and the equilibrium solubility.
This significantly affects the bioavailability of the drug.
How is kinetic solubility of a drug determined?
1) Dissolving the drug in dimethyl sulfuric (DMSO).
2) Add water until a precipitate forms.
3) Samples are filtered to remove the precipitate.
4) Concentrations are measured using UV or LC/MS.
How is thermodynamic and equilibrium solubility determined and what is its importance?
1) Dissolved in an aqueous medium for a prolonged period of time until an equilibrium is achieved under constant agitation and desired temperature.
2) Sample is filtered
3) Drug concentration is analysed using UV or LC/MS.
This helps to identify the polymorphic and amorphous forms of the drug.
What does the partition coefficient (oil/water) indicate and how is it determined?
It indicates the lipophilicity of a drug and is determined by the shake flask method using 2 immiscible solvents: water (or phosphate buffer at pH 7.4) and octanol. Defined as the ratio of un-ionised drug distributed between the organic phase (C organic) and aqueous phases (C aqueous) at equilibrium.
Ko/w= (C organic/C aqueous)
How does the drug’s Ko/w value affects its absorption?
Higher Ko/w values increases a drugs ability to cross cell membrane due to its lipophilicity, which enhances passive absorption. However, too high of a lipophilicity can lead to low solubility. Thus, a balance between lipophilicity and solubility is ideal for optimal drug absorption.
Why is dissolution important in drug absorption?
It reveals the rate and extent of a drugs absorption in the body. It is the process where the drug substances (solute) dissolves into the solution, with the dissolution rate indicating how fast it dissolves in a given medium.
What is the primary objective of stability testing in drug development?
Provides info such as processing, storage, and absorption at gastrointestinal mucosa. Preformulation stability studies cover solid-state, solution phase stability, physical stability & photostability studies. Solid state stability testing are performed when samples are exposed to extreme temp and humidity -provides info on possible routes of degradation, & degradation products of the drug substances.
What is drug formulation, and what does the process involve?
Process of determining the best way to deliver and Active Pharmaceutical Ingrediant by combining it with inactive substances to create a final product. During development, formulations are tested for stability, efficiency, & processability. Most drugs are developed as tablets/capsules, with some s njections, depending on drug-specific needs. After formulation, preclinical + clinical studies assess safety + efficacy, followed by manufacturing under GMP.
What function does the excipient binders have?
Substances that promotes cohesiveness of powders thereby providing the mechanical strength to the tablet.
What function does the excipient diluents have?
Insert substance used as a filler to provide the required bulk of the tablet & it also provides better tablet properties.
What function does the excipient lubricants have?
An additive to reduce friction during tabletting. It also helps tablet to overcome various defects like lamination, sticking & chipping.
What is the function of the excipient glidant?
Used to improve powder flow properties of the formulation.
What is the function of the excipient disintegrant?
Used in solid dosage forms to break up a dosage form after oral administration, hence it contribute to increase in surface area and thereby faster dissolution.
What is the function of the excipient flavours?
Incorporated into formulation to mask the unpleasant tasting API.
What is the function of the excipient colouring agents?
Added to impart colour to the formulation to identify new formulation & to ultimately increase patient compliance.
What is the function of the excipient coating materials?
A covering over a tablet to protect drug from environment (oxygen/humidity), to mask taste or odour of drug substances, modifying drug release profiles.
What is the function of the excipient adsorbent?
Used into formulation to adsorb the semisolid or liquid excipients.
What is the function of the excipient antioxidant?
Added to tablet formulation to delay or inhibit the oxidation process.
What are the main methods of tablet formulation?
Tablet formulation methods are divided into direct compression and granulation. Tablet dosage forms unit operations are determined according to which manufacturing techniques been applied. This includes: feeding, blending, milling granulation, drying, compression/encapsulation & coating.
What is direct compression and what are the steps?
Direct compression (DC) is the process of compressing tablets directly from a powder blend of the API, excipients, and lubricant, without additional mechanical treatment. This method simplifies processing. Key steps in DC include:
Milling of APIs and excipients
Mixing of APIs and excipients
Tablet compression
What are the advantages of direct compression?
- Economical: Fewer unit operations reduce costs.
- Less process validation and lower energy consumption.
- Negligible batch-to-batch variation.
- Ideal for moisture- or heat-sensitive APIs due to no moisture or heat treatment.
- Tablets produced have good hardness and friability.
What are the disadvantages of direct compression (DC)?
- Can’t be used for all API’s, especially high-dose API’s with poor flow and compaction properties, and low-dose API’s where uniformity is challenging.
- Poor flowabilty due to particle size, shape, & distribution, though particle engineering can help.
- Risk of segregation, which require careful excipient selection & mixing.
- High cost of excipients due to strict quality requirements for DC.
What is granulation, and why is it used in tablet formulation?
A process of particle enlargement by agglomeration, used when a powder blend cannot be directly compressed into tablets. It enhances flowabilty & reduces dust, making it a common technique in oral solid dosage manufacturing.
What are the main reasons for using granulation in tablet formulation?
- Improve flow properties of the powder.
- Narrow particle size distribution.
- Enhances compactability.
- Increase powder density.
- Prevent segregation.
- Ensure uniformity and homogeneity.
- Control the drug release rate.
What is the dry granulation process, and when is it used?
Used for API’s that are sensitive to solvents, heat and moisture. It offers better flexibility over direct compression and is more cost effective than wet granulation. It involves mechanical compression or compaction to form particle agglomerates without needing heat or moisture.
What methods and steps are involved in the dry granulation process?
Can be done by roller compaction or slugging and involves:
* Milling API’s and excipients.
* Blending the powder mix.
* Compressing into slugs or ribbons.
* Milling to desired particle size.
* Mixing with lubricant and disintegrating agents.
* Tablet compression.
Feeders are used for continuous manufacturing.
What is wet granulation, and what are the steps involved in the process?
Involves wet massing the API & excipients with a granulation liquid (usually water, sometimes ethanol) followed by sizing & drying. Steps include:
* Milling of APIs and excipients
* Mixing of the powder blend
* Agglomeration (mixing binder solution with powder)
* Drying of moist granules
*Milling dry granules with lubricant, disintegrant, and binder
*Mixing screened granules with lubricant & disintegrant
* Tabletting
What are the advantages of wet granulation?
- Improved bulk density & flowabilty of the powder mix.
- Prevention of API segregation, leading to better mixing homogeneity.
- Even colour distribution.
- Easier handling of fine or dusty powders.
- Enhanced compressibility due to polymeric binder solution.
- Improved dissolution of hydrophobic drugs.
What are the disadvantages of wet granulation?
- Requires multiple expensive equipment & a large space.
- Time-consuming & complex due to multiple unit operation (wetting+drying).
- Higher costs due to the energy-intensive drying phase.
- Not suitable for moisture & heat sensitive API’s.
What is high shear granulation, and what equipment is used?
Performed in a closed container with a cylindrical or conical vessel, a chopper, a jacket, and heating/cooling control.
It involves mixing, spraying binder liquid onto a powder bed, granule attrition, and breakage followed by drying.
What process variables can affect the high shear granulation process?
- Impeller and chopper speed.
- Load of the vessel.
- Granulating solution addition take and method.
- Mixing time.
What are the advantages of high shear granulation?
- Short granulation time.
- Ability to handle highly viscous materials.
- Less binder solution required.
- Predictable granulation end point.
What are the disadvantages of high shear granulation?
- Mechanical degradation (fragile particles).
- Not suitable for thermo-labile powders.
- Over-wetting can lead to larger granules.
What is fluidised bed granulation, and what equipment is involved?
Involves a fluidised bed dryer with components like an air-handling unit, product container, air distributor, exhaust fan, control system, solution delivery system, and spray nozzle.
The process starts by fluidizing a powder mix in heated air, followed by spraying a liquid binder onto the powder bed and drying.
What process factors affect fluidised bed granulation?
- Fluidising air flow rate/gas velocity.
- Liquid binder spray rate.
- Atomisation air pressure.
- Inlet process air temperature.
What are the advantages of fluidised bed granulation?
- Continuous drying.
- No need for wet screening.
- Suitable for subsequent coating & controlled-release products.
What is the disadvantage of fluidised bed granulation?
Potential problems with reproducibility.
How is a drug molecule introduced to the body, and how does the route of administration (RoA) affect its effectiveness?
- Drug must be introduced into the body via suitable RoA.
- For localised effects, drugs are administered topically (creams, eye drops, inhalers).
- For systematic effects, drugs are administered enterally via GI tract (oral) or parenterally via route other than GI tract (injection).
- Drug must be in an appropriate dosage form (tablet, capsule, solution) & be soluble in the required fluid (GI tract, blood).
What are Cmax, Tmax, and AUC in pharmacokinetics?
- Cmax: The peak concentration of a drug observed after administration.
- Tmax: The time after administration when maximum plasma conc is reached, where the rate of absorption equals the rate of elimination.
- AUC (Area Under Curve): Represents the total drug exposure over time.
What are MEC and MTC, and why are they important in assessing drug action?
- MEC (Minimum Effective Concentration): The lowest conc at which the drug is effective; levels above this threshold show therapeutic effects.
- MTC (Maximum Tolerated Concentration): The highest conc that can be tolerated without adverse effects.
- These values help determine the onset time and duration of action of the drug.
What is the significance of keeping drug concentration below 80% maximal response?
Increasing conc beyond 80% maximal response typically offers minimal additional therapeutic effects but raises the risk of adverse effects.
What factors affect the dissolution of a solid dosage form?
- Solubility at the gastric pH, influenced by the drugs molecular structure and polymorphic form.
- Particle size and solid form.
- Concentration in solution, as described by the Noyes-Whitney equation.
What equation describes the dissolution rate?
Dissolution Rate= K A (Cs - C)
K= constant
A= surface area
Cs= solubility
C= concentration in solution
What are “sink” and “non-sink” dissolution behaviours in drug absorption?
- Sink Dissolution: when the solute is removed from the dissolving medium faster than it dissolves, often due to drug absorbed faster than it dissolves.
- Non-Sink Dissolution: when the dosage form dissolves so quickly that the drug cannot be absorbed fast enough, causing drug accumulation in solution, which slows down dissolution.
- Dissolution rate is crucial in determining how quickly the drug becomes available to the body.
What are tablets in solid oral dosage forms and what are their different types?
This is where the (API) is combined with excipients (binders, disintegrants) & compressed into a hard pellet. Types include:
- Fast-acting, slow release, controlled release
- Enteric-coated, film-coated
- Sublingual, chewable, buccal, and wafers
What are capsules, and what is the difference between hard and soft gelatin capsules?
Capsules contain the API mixed with excipients:
- Hard Gelatin Capsules: Contain API and excipients as powders inside a gelatin shell.
- Soft Gelatin Capsules: Contain the API in a liquid formulation.
What are modified solid oral dosage forms and what does “Modified Release” (MR) mean?
Designed for targeted delivery (enteric-coated tablets) or sustained/controlled release of the API. “Modified Release” (MR) can indicate gastro-resistant or prolonged release, but it’s a general term and not specific for one type of release.
What are enteric-coated tablets, and how do they work?
Contain a coating insoluble in stomach acid, protecting the drug from degradation in the stomach.
The coating dissolves in the higher pH of the intestine, allowing the drug to be released there. These are also called delayed release dosage forms and may be labeled as EC (Enteric Coated) or GR (Gastro Resistant).
What are the categories of drug release, and what do they mean?
- Delayed Release: drug is released later time.
- Repeat Action: initial dose released soon after administration,subsequent doses released at intervals.
- Prolonged Release: absorbed over a longer period of time.
- Sustained Release:provides initial therapeutic dose soon after,followed by gradual release overtime
- Extended Release: maintains therapeutic plasma levels for long time (8-12 hrs).
- Controlled Release: released at constant rate, keeping plasma conc steady overtime.
What are the different forms of liquid oral dosage forms?
- Solutions: API is dissolved in a liquid.
- Suspensions: solid particles of the API are mixed into a liquid.
- Emulsions: suspensions involving one liquid in a second liquid with which the first will not mix.
- Syrups: high concentration of sucrose or sugar to sweeten for ease of use.
- Elixirs: contain between 5-40% alcohol
What is the difference between suspension and emulsion?
- Suspension: solid drug in liquid vehicle.
- Emulsion: liquid drug in liquid vehicle
1) oil in water emulsion (o/w)
2) water in oil emulsion (w/o)
What are the different types of suspensions?
- Oral: given through oral route therefore they contain flavouring & sweetening compounds for masking of bitter taste of drug.
- Topical: applied on external surface of body
- Parenteral: administered through parenteral routes like intravenously/intramuscularly.
- Ophthalmics: used to treat eyes disorder
What are the applications of pharmaceutical suspensions?
- Suitable for people who have difficulty in swallowing solid dosage forms.
- For quicker absorption rate of drug from GI tract as drug is delivered in finely divided form.
- Useful for drugs with low solubility.
- Stability for unstable drugs
What are the core ingredients for a pharmaceutical suspension?
- API
- Suspending agents.
- Wetting agents
- Solvents, buffers, anti-foaming agents
- Flocculating agents, preservatives, antioxidants
- Colouring agents, flavouring agents, sweetening agents.
How is a tablet or capsule converted to a liquid in an extemporaneous compounding?
- Tablet or capsule is crushed in a mortar.
- Mixing with a small amount of vehicle to form a paste.
- Gradually adding the rest of the vehicle until fully incorporated.
What are the 2 forms of delivering a drug via the rectal route?
- Rectal Suppositories: solid/semi-solid, melt at body temperature to release the drug.
- Enemas: API suspended in solution & infused into the rectum.
What are the advantages and disadvantages of the rectal route for drug delivery?
+: Useful for patients unable to to swallow (unconscious, vomiting, GI issues); can avoid local adverse reactions.
-: Poor adherence due to potential for local irritation of the rectal mucosa.
What are the major parenteral routes?
- Intravascular- Placing a drug directly into the blood stream.
- Intramuscular- Injected into the skeletal muscle.
- Subcutaneous- Absorption of drugs from the subcutaneous tissues.
- Transdermal- Absorption through the skin (percutaneous).
- Inhalation- API to the local site of action in the lungs, or absorption through the respiratory system.
What is the importance of chemical kinetics and what is the equation?
- Determines drug stability under various conditions.
- Used in stability testing to assess how quality changes over time due to temperature, humidity, and light.
- Helps determine a drugs shelf life.
- Rate= change in conc/ time for change to occur.
What are some pharmaceutical examples of 0 order processes?
- Slow release formulations: constant amount of drug released per unit time.
- Slow intravenous infusion: provides a constant rate of drug delivery.
- Drug stability: decomposition of active drugs in the solid phase/in suspension
What is the definition of half-life of a 0 order reaction?
The time taken for 1/2 of the reactant to decompose. Half life is dependent upon the concentration.
What is the definition of shelf-life?
This is typically the time taken for a drug to decompose to 90% of its initial concentration (or the time for 10% of the drug to decompose).
This is used to determine how long a drug is fit for use.
What is the difference between passing shelf-life and expiration date?
- Passing shelf-life might be safe for consumption but quality is no longer guaranteed.
- Passing expiration date (shortly after), may contain some potency and may be safe as expiration date guarantees full potency and safety of the drug.
What are the factors affecting drug stability, accelerating the decomposition of drugs?
- pH: store at optimum pH
- Temperature: store at an appropriate temperature.
- Hydrolysis and oxidation reaction
- Light: photochemical reactions. Store drug in containers which exclude UV light.
- Moisture: problem for stability of solid dosage forms, suitable packaging is required. Excipients may also increase moisture content & increase drug decomposition rates.
What is the difference between primary, secondary and tertiary packaging?
- Primary: has direct contact with the product (bottle, cap, liner and bears appropriate labelling with content & usage info.
- Secondary: a pack component which has no product contact but provides extra physical protection to primary pack
- Tertiary: transportation in bulk (cartons from warehouse)
What are the clinical trial phases?
- Pre-clinical trials: lab and animal studies
- Phase 1: safety study on small group (typically 10s)
- Phase 2: safety study on large group (100s), identify side effects, measure effectiveness.
- Phase 3: measure effectiveness, monitor side effects, compare to current treatment and placebo’s-on large groups (1000s).
- Phase 4: Monitor long term side effects.
What is involved in the life cycle of a medicine?
- Discovery of a drug
- Manufacture of the drug
- Packaging and distribution of the medicine.
- Administration of the medicine to/by patients
- Excretion of drug or metabolites via urine/faeces
- Disposal of drug or metabolites via sewage system
- Disposal of drug (possible recycling) of unused/expired medicines
What is E factor?
This is a way of assessing environmental impact of drug manufacture and defined as the number of Kg of waste produced for each Kg of drug produced.
What is supply chain management?
This is the management of the interconnection of organisations that relate to each other through upstream (those on the manufacturing side) and downstream (those closer to the customer/user/patient) linkages between the processes that produce value to the customer in the form of products and services.
What are Antimicrobials?
These are medicines used to prevent and treat infectious diseases in humans, animals, and plants including antibiotics (bacteria), antivirals (viruses), antifungals (fungi) and antiparasitics.
What are antimicrobial resistance (AMR)?
AMR occurs when bacteria, viruses, fungi, and parasites no longer respond to antimicrobial medicines, making infections harder to treat, increasing disease spread, severe illnesses, disability, and death.
What is antimicrobial stewardship (AMS)?
This is a healthcare approach to promote and monitor the judicious use of antimicrobials to preserve their effectiveness.
