Pharmaceutical Powders and Mixtures Quiz

Powder Flow and Density

• Powdered solids are heterogeneous mixtures of particles with various sizes and shapes, dispersed with air spaces.
• Mass-to-volume relationships in powders are complex due to the presence of open intra-particulate voids, closed intra-particulate voids, and inter-particulate voids.
• True volume (Vt) excludes all spaces and is determined using helium pycnometry.
• Granular volume (Vg) includes all intra-particulate voids.
• Bulk volume (Vb) is the total volume occupied by the entire powder mass.
• Tapped volume (Vtapped) is the volume after mechanical tapping or compression, which reduces void spaces and increases packing density.
• Void volume is the space between particles in the bulk powder (Bulk Volume - True Volume).
• Porosity is the percentage of space within a material (Volume of Voids / Total Volume) x 100.

Volume Measurement Techniques

• X-ray diffraction method
• Helium pycnometer (measures volume using a non-adsorbing gas like helium in a sealed system).
• Specific gravity bottle method (usually for granules, using nonsolvent liquids or mercury).
• Cylinder method (for measuring volume).

Determination of Density

• Bulk density is the ratio of mass to the volume, including inter-particulate voids volume of an untapped powder sample.
• It depends on the particles' density and arrangement in the powder bed.
• Tapped density is the increased bulk density achieved after mechanically tapping a container containing the powder sample.

Applications

• Analyzing bulk and tapped densities provides insights into compressibility index and Hausner ratio.
• It helps understand powder flowability and compressibility.

Powder Flowability

• Flowability is a powder's ability to flow.
• It influences pharmaceutical processes like mixing, transferring, and compression.
• Poor flowability can lead to problems during these processes.

Compressibility Index and Hausner Ratio

• These are measures of a product's settling ability and the importance of inter-particulate interactions.
• In a free-flowing powder, these interactions are less significant, and bulk and tapped densities are closer.
• Poorly flowing materials show greater inter-particulate interactions and a larger difference between bulk and tapped densities.
• Formulas for Compressibility Index and Hausner Ratio are provided.
• Tables relate Hausner ratio to flow character and compressibility index.

Factors Affecting Powder Flow

• Particle size
• Particle shape
• Particle density
• Porosity
• Surface texture

Angle of Repose

• Angle of Repose is the angle between the horizontal and the plane of contact between two bodies when the upper body is just about to slide over the lower body (angle of friction).
• Values of angle of repose provide information about flow properties.

Particle Size Analysis

• Particle size is a critical process in the pharmaceutical industry, influencing drug properties like efficacy, stability, dissolution rate, bioavailability, formulation design, and drug release.
• Particle size can be determined by sieving using predefined mesh sizes.
• Equivalent sphere diameter is a concept in particle size analysis, describing irregularly shaped particles as perfect spheres based on a specific measured property.
• Methods like Feret's diameter and Martin's diameter help characterize particle size for irregularly shaped particles.

Particle Size Analysis Techniques

• Laser Diffraction (LD): measures particle size distribution (0.01 μm to several mm) based on light scattering.
• Dynamic Light Scattering (DLS): best for submicron particles (nanometer range), measuring Brownian motion in a liquid medium.
• Microscopy (optical and electron): used for larger (>1 μm) and nano-sized particles, providing morphological information.
• Sieving: a traditional method for particles larger than 75 μm, involving passing particles through sieves with decreasing mesh sizes.

PDI (Polydispersity Index)

• PDI is a dimensionless value quantifying the uniformity or heterogeneity of particle sizes in a sample.
• Low PDI indicates a narrow size distribution (monodisperse system).
• High PDI indicates a broad size distribution (polydisperse system).
• Calculated from cumulant analysis of the correlation function, providing information about particle size variability.
• A table provides PDI scale values and their corresponding flow characteristics.

Procedure for Particle Size Analysis

• Weigh a specified amount of powder (e.g., 50g) using analytical equipment.
• Utilize a machine to vibrate the sample through the varying mesh sizes in the sieve.
• Weigh the material retained in each sieve to determine the percentage distribution.

Formulation of Parenteral Products

• Parenteral administration means administering medications into tissues or circulatory systems through injection.
• Types of parenteral preparations include solutions, suspensions, emulsions, powders, and gels.
• Routes of parenteral administration are Intravenous (IV), Intramuscular (IM), Subcutaneous (SC), Intradermal (ID), Intraspinal (IS), Intra arterial (IA).
• Requirements for parenteral preparations include sterility, purity, a lack of pyrogens, stability, and isotonicity.
• Containers and closures include ampoules, vials, syringes, cartridges, bottles, and bags.
• Ampoule sealing techniques include tip sealing and pull sealing.

Mixing and Homogenization

• Mixing combines two or more components so particles are positioned as closely as possible.
• Homogenization aims to create a uniform mixture and is less common.
• Mixing, in powders, is a chance process, and perfect mixing is frequently impossible.

Segregation

• Segregation is the opposite of mixing; components may separate.
• Factors affecting segregation include particle size, shape, density, and flow characteristics.

Factors Affecting Particle Size Reduction

• Material properties (Hardness, Moisture Content, Elasticity, Heat Sensitivity).
• Milling Technique (Ball milling vs Hammer milling).
• Milling Parameters (Speed and Rotation, Temperature, Milling Time, Feed Rate).
• Volatile or unstable materials require specialized milling techniques (e.g., cryogenic milling) to prevent degradation.

Procedure for Particle Size Reduction

• Weigh a specified amount of coarse substance and grind it with a mill for different time durations.
• Use a sieve to separate the resultant finer particles from the coarse portions.
• Weigh the finer substance to establish a relationship with milling time.

Preparation of Eye Drops

• Eye drops are topical applications for treating eye surface or intraocular conditions.
• Typical conditions include bacterial, fungal, viral infections, allergic or infectious conjunctivitis, inflammation, elevated intraocular pressure, and glaucoma, and dry eye.
• Excessive volume considerations are vital; a typical drop has much of its volume lost.
• Eye drops need sterility, preservation, isotonicity, buffering, viscosity, ocular bioavailability, and suitable packaging.

Effervescent Granules

• Effervescent granules release carbon dioxide when dissolved in water due to chemical reactions between acid and base.
• They contain at least one acid and one base (e.g., citric and tartaric acid with sodium bicarbonate).
• This mixing results in a fizzy effervescent effect.
• Granules, instead of fine powders, are preferable to slow the reactions down to prevent overflow.
• Wet and dry methods are used for preparation.

Drying

• Drying removes solvents (e.g., water) to create a dry solid product.
• Crucial in maintaining stability and quality for various pharmaceutical formulations.
• Drying methods consider factors such as moisture content and material sensitivity.
• Various techniques exist (e.g., fluidized bed, spray, freeze, vacuum drying) to adjust parameters like time, temperature, and scale.

Moisture Content Determination

• Methods include loss on drying, Karl Fischer titration, infrared moisture analysis, thermogravimetric analysis, dielectric moisture meters, microwave drying, and distillation.
• Different moisture content (bound vs free) aspects are considered.
• Equilibrium moisture content (EMC) is the moisture level a material reaches in balance with its surrounding environment.

Procedure for Measuring Moisture Content

• Weigh a sample (e.g., MCC or lactose) and wet it with water.
• Dry the sample in an oven at varying time points.
• Weigh the sample repeatedly to determine the loss on drying and moisture content.
• Plot a graph of moisture content against time.

Test your knowledge on fundamental concepts related to bulk density, particle size, and powder flowability in pharmaceuticals. This quiz covers key terms like the compressibility index, Hausner ratio, and factors affecting powder mixtures. Enhance your understanding of materials utilized in pharmaceutical formulations.