Questions and Answers
What must be maintained at 37±0.5°C in the flow-through cell?
The paddle-over-disk apparatus maintains sink conditions.
True
What is the maximum volume for the dissolution medium in the flow-through cell?
250 ml
Which of the following apparatus uses a rotating shaft for drug testing?
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In the content uniformity test, a relative standard deviation (RSD) of less than __% indicates that the sample passes.
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Match the following methods with their descriptions:
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What is the use of the reciprocating holder apparatus?
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Which of the following is true regarding the rotating cylinder?
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What is one purpose of solid dosage forms?
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Which of the following is NOT a type of solid dosage form?
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The resistance of tablets against mechanical shock is referred to as friability.
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What is drug dissolution?
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The estimated number of people in the United States with difficulty swallowing is over ______ million.
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What can be a consequence of larger tablets and capsules?
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What does friability measure in tablets?
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What is the purpose of the hardness test for tablets?
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What is the maximum acceptable percent loss of mass for most products during friability testing?
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What does the term 'disintegration' refer to?
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What affects drug dissolution in a solid dosage form?
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Salt formation is a common approach used to decrease drug solubility.
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What is the significance of the dissolution rate in pharmaceuticals?
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What is a solvate?
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What is it called when the solvent of a solvate is water?
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Anhydrous compounds are less soluble than hydrate compounds.
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Which factor greatly influences the solubility of weak acidic and weak basic drugs?
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What is intrinsic solubility?
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Which substance can interfere with the absorption of drugs when administered together?
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What is the impact of polymorphism on drugs?
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Metastable polymorphs have lower melting points and higher aqueous solubility compared to stable polymorphs.
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Match the following with their effects on drug dissolution:
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How do surfactants enhance the dissolution rate of poorly soluble drugs?
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The __________ method is considered superior in granulation for enhancing drug dissolution.
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Dissolution testing is essential for evaluating the bioavailability of drug products.
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What is the primary purpose of dissolution rate testing?
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Which apparatus type is not used in dissolution testing?
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Study Notes
Pharmaceutical Preparation and Dosage Forms
- Completed forms include tablets, capsules, granules, and powders containing prescribed doses of medication.
- Key features of dosage forms: accurate dosing, protection from environmental factors, gastric juices, taste masking, sustained and controlled release, optimal drug action, and drug delivery to body cavities.
Tablets
- Solid dosage forms with one or more active ingredients; can be coated or uncoated.
- Common applications: oral, implants, injections, irrigation, vaginal use.
- Appearance parameters: size, shape, color, odor, and surface texture.
Physical and Chemical Tests for Tablets
- Physical tests include disintegration, weight variation, hardness, friability, and thickness.
- Key chemical tests: drug content or assay, content uniformity, and dissolution tests.
Issues with Swallowing Tablets
- Dysphagia affects over 16 million people in the U.S., leading to treatment noncompliance.
- Tablet size and shape significantly influence esophageal transit time and can cause discomfort or injury.
Research on Tablet Transit Times
- 8 mm tablets have shorter transit times compared to 11 mm and 14 mm tablets, indicating size affects swallowing and patient compliance.
Tablet Hardness and Friability
- Hardness measures a tablet's resistance to crushing; important for ensuring mechanical integrity and handling.
- Friability indicates weight loss due to mechanical action, influencing appearance and potential dosing errors.
- Acceptance criteria typically require a loss of mass not greater than 1%.
Friability Testing Procedure
- Conducted using a Roche Friabilator, where tablets tumble in a drum to evaluate abrasion during transport.
- Specifications vary for different tablet types (effervescent, hygroscopic).
Hardness Testing
- Hardness tests determine the breaking force; various testers are used, with manual and mechanical options available.
- Important factors include amount of binder, compression force, and granulation method.
Acceptance Criteria for Hardness
- A minimum force of 5-8 kg is required for satisfactory tablet integrity.
Quality Control in Tablet Production
- Quality tests ensure tablets have uniform physiochemical properties like diameter, thickness, and hardness for consistent pharmacological effects.
Key Factors in Thickness and Diameter
- Influenced by tablet compression, amount of material, and die dimensions.
- Acceptance criteria allow deviations of ±5% for smaller tablets and ±3% for larger ones.
Dissolution Process
- Defined as the transfer of a solid solute into a solution, crucial for drug absorption.
- Influenced by disintegration and the area of contact between solid and liquid.
Mechanisms of Dissolution
- The overall rate depends on disintegration and solubilization, with cohesive properties being key in solid dosage forms.
Dissolution Rate Theories
- Three key models: diffusion layer model, Danckwert's model, and interfacial barrier model - each explains dissolution dynamics and rate dependence on formulation characteristics.
Factors Influencing Dissolution
- Drug solubility, particle size, salt formation, solvates and hydrates, pH effects, and co-precipitation significantly affect drug release and absorption.
Key Properties Affecting Drug Dissolution
- Solubility: Minimum 1% aqueous solubility is required to avoid absorption issues.
- Particle Size: Smaller sizes enhance surface area but can affect solubility rates.
- pH Effects: Solubility of weak acids and bases depends on their pKa and the dissolution medium's pH.
Summary of Drug Dissolution Factors
- Proper formulation and testing are essential for effective drug delivery and maximized patient outcomes.### Polymorphism and Amorphism
- Polymorphism refers to substances existing in multiple crystalline forms, known as polymorphs.
- Stable polymorphs are characterized by lower energy states, higher melting points (M.P.), and reduced aqueous solubility.
- Metastable polymorphs have higher energy states, lower melting points, and increased aqueous solubility, which can enhance dissolution rates.
- Metastable forms can be obtained through methods like recrystallization, melting, or rapid cooling.
- Polymorphism affects drug solubility, dissolution rate, and overall bioavailability, though enhanced dissolution does not always lead to improved bioavailability.
Complexation
- The complexation of drugs with gastrointestinal (GIT) fluids may modify the absorption rate and extent.
- Examples of drugs affected by complexation include streptomycin and tetracyclines.
Factors Related to Drug Product Formulation
Diluents
- Increased starch content (5-20%) in salicylic acid tablets leads to a threefold increase in dissolution rate by enhancing hydrophilicity and surface area.
- The ratio of drug to excipient affects dissolution rates, as seen with quinazoline compounds.
Disintegrants
- Disintegrants added pre- and post-granulation influence dissolution rates.
- Microcrystalline cellulose disintegrates well but can impede dissolution under high compression forces.
- Starch serves both as a diluent and an effective disintegrant due to its swellability and hydrophilic nature.
Binders and Granulating Agents
- Hydrophilic binders can improve dissolution rates of poorly soluble drugs.
- Excess binder may increase tablet hardness, reducing dissolution rates.
- Gelatin provides faster dissolution in human gastric juice for some tablets compared to other binders like Na-carboxymethyl cellulose.
Lubricants
- Hydrophobic lubricants (metallic stearates, waxes) can inhibit wettability, leading to decreased disintegration and dissolution.
- Soluble lubricants (e.g., SLS, Carbowaxes) enhance drug dissolution.
Surfactants
- Surfactants increase the dissolution rate of poorly soluble drugs by lowering interfacial tension and enlarging effective surface area.
- Non-ionic surfactant Polysorbate 80 effectively improves the dissolution rate of phenacetin granules.
Effect of Coating
- Coating materials, particularly shellac and CAP, significantly impact the dissolution rate of coated tablets, with HPMC-coated tablets showing better profiles than MC-coated ones.
Processing Factors of Formulation
Method of Granulation
- Granulation generally enhances the dissolution rate of poorly soluble drugs.
- Wet granulation is often superior, but exceptions exist, such as sodium salicylate tablets that dissolve more rapidly via direct compression.
- The APOC method produces stronger tablets with higher dissolution rates due to increased internal surface area.
Compression Force
- Compression affects tablet density, porosity, hardness, disintegration, and dissolution rates.
- Higher compression can lead to deformation or fracture of drug particles.
Drug-Excipient Interaction
- Interactions during processing steps (mixing, milling, blending) can influence dissolution rates.
Storage Conditions
- Aging of hydrochlorothiazide tablets showed decreased dissolution rates, while PVP granulations remained stable at elevated temperatures.
Factors Relating to Dissolution Apparatus
Agitation
- The relationship between agitation intensity and dissolution rate varies with agitation type and the physical/chemical properties of solids.
- Maintaining low agitation speeds is essential for reproducible results.
Stirring Element Alignment
- Accurate alignment of stirring elements can significantly affect dissolution rates.
Sampling Probe Position
- Proper positioning of the sampling probe is crucial to maintain consistent hydrodynamics and dissolution rates.
Factors Relating to Dissolution Test Parameters
- Temperature control is critical as drug solubility is temperature-dependent.
- The nature of the dissolution medium (pH, viscosity, surface tension) influences the drug release dynamics.
Dissolution Testing
- Dissolution tests measure the rate and extent of drug release from solid dosage forms in aqueous media under controlled conditions.
- It is essential for assessing bioavailability, batch uniformity, product quality, and stability.
Types of Dissolution Apparatus
- Several apparatus types are employed (e.g., Basket, Paddle, Reciprocating Cylinder) with specifications for rotation speed, design, and usage for various dosage forms.
Advantages and Disadvantages of Apparatus Types
- advantages of specific systems include ease of automation and pH alteration during tests, while disadvantages may include clogging, complex hydrodynamics, and limitations in volume or experience.
Summary of Specific Apparatus Functions
- Each apparatus type serves particular drug forms (tablets, capsules, patches) and is designed to facilitate controlled dissolution testing with conditions tailored to specific pharmacological properties.### Solid Dosage Forms and pH Profile
- Solid dosage forms utilize various methods for dissolution testing, crucial for understanding drug release dynamics.
- Testing conditions often target specific temperature and pH levels.
Rotating Cylinder Method
- Utilizes a modified apparatus with a stainless steel cylinder in place of a basket and shaft.
- Maintains temperature at 32±0.5°C, ensuring consistency during experiments.
- Dosage units are placed externally on the cylinder to minimize trapped air and enhance dissolution results.
- Samples for analysis are drawn from a defined zone between the dissolution medium and cylinder surface.
- Advantages: Can repurpose existing apparatus, minimizing cost.
- Disadvantages: Requires large volumes of dissolution medium, potentially diluting the drug and complicating analysis; cleaning the cylinder is difficult.
Reciprocating Holder Method
- The setup includes a flat-bottomed cylindrical vessel containing the dissolution medium and a disk-shaped holder for samples.
- Maintains temperature at 32±0.5°C with a reciprocation frequency of 30 cycles/min.
- Agitation is generated through a vertical reciprocating motion.
- Allows maintenance of sink conditions for improved sensitivity in testing.
- Advantages: Flexibility in medium volume selection; enhanced sensitivity.
- Disadvantages: Higher initial investment due to unique design requirements.
Unofficial Methods of Dissolution Testing
- Various methods exist beyond standard tests, such as:
- Rotating/Static Disk Method: Drug compressed in a non-disintegrating disc, with one face exposed to dissolution medium. Monitors intrinsic dissolution rate.
- Beaker Method: Utilizes 0.1N HCl at 37°C in a beaker agitated by a three-blade stirrer.
- Flask Stirrer Method: Similar to the Beaker Method, but employs a round-bottom flask (RBF) to prevent mold formation.
- Peristalsis Method: Simulates GI tract conditions, using rigid tubing to pump dissolution medium through drug.
- Rotating Bottle Method: Capped bottles rotate in a temperature-controlled bath, allowing for sample decanting.
- Dialysis Method: Reflects dynamic interactions of drug release, involving suspended cells in water at precise agitation rates.
- Diffusion Cell: Characterizes drug permeation from topical products; includes static and flow-through systems with skin models.
Content Uniformity Test
- Ensures equal amounts of active pharmaceutical ingredients in each dosage form of a batch.
- Primarily applied to tablets and capsules for consistency in drug delivery.
Testing Standards and Procedures
- Content uniformity testing is validated through specific assays of randomly selected units.
- Major pharmacopoeias include IP, BP, USP, and Ph.Eur. guiding testing standards.
United States Pharmacopoeia (USP) Procedure
- Stage 1: Sample 10 units; test passes if RSD < 6% and all values are between 85% and 115%.
- Stage 2: If one unit is outside 85%-115% but within 75%-125%, sample an additional 20 units. The complete batch passes if RSD < 7.8% and fails one unit condition.
Relative Standard Deviation (RSD)
- RSD quantifies variability relative to the mean in analytical chemistry contexts.
- Calculated as (Standard Deviation / Average) * 100, expresses precision and repeatability of assays.
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Description
This quiz explores the completed forms of pharmaceutical preparations that include prescribed doses of medication. It covers various aspects such as dosage accuracy, protection mechanisms, and drug delivery methods to ensure optimal therapeutic effects. Test your knowledge on how these forms impact drug action and patient care.
