Density Measurement methods / Density measurement methods for solids / rheology physical pharmacy notes PDF

Density Measurement methods

1. Rotating Cylinder method 

2. Tilted Box method 

3. Fixed Cone Method

Relation between angle of repose and type of flow and type of powder

Grades of powder 

Factors Affecting Flowability Particle size and particle size distribution

• Addition of small particle to larger particle which fill the void space reduce inter particles cohesive force and reduces surface rugosity and acts as lubricant.
•  Presence of particle of size smaller than 10 micron gives stickiness to material.

Particle shape and surface roughness

• Spherical shape is the best shape which gives the maximum flow rate. 
• Irregular shape of particle in material causes the bridging in hopper. 
• Roughness on the surface can cause mechanical hindrance to the flow of material.

Example: Spray-dried lactose has good flowability because of the produced near spherical shape. 

Density and porosity

• More density and less porosity give better flow. 

Hygroscopicity

It reduces flow rate, because it increases adhesive and cohesive forces between particles.

Electrostatic charge

• More electrostatic charge so reduced flowability.

Methods of Improvement of Flowability

(a) By addition of glidant

• Flow can be improved by reducing adhesion and cohesion. 
• Effectiveness of glidant is found to be dependent on particle size of material to which it is added.
• E.g., corn starch is more effective in coarser particle.  

Talc, silicon dioxide and Mg-stearate are effective in finer particles. There are two types of silicon dioxide: (i) Hydrophilic (ii) Hydrophobic–more effective as glidant independent of mixing condition.

(b) By size reduction or by addition of fine particles

• Both should be up to optimum limit 
•  Addition of fine particles to certain level improves flow. 

(c) By wet granulation

• Gives regular shape and also removes the static charge of powder surface, thus improves the flow.

(d) By removing static charge. 

(e) By densification with the help of slugging. 

(f) By using auger feed equipment. 

(g) By addition of flow activator

Powder flow property is impaired through increased moisture content of very fine MgO and may be used as a flow activator. MgO adsorbs water surrounding the moist particle.

(h) For hygroscopic and moist powder

Use of silicon treated powder such as silicon coated talc or Na-bicarbonate may also be beneficial in improving the flowability of moist and hygroscopic powder.

(i) By alterations of process condition 

•  Used vibration assisted hopper 
•  Used force feeder

(j) By use of spray drying 

• Advantose 100 maltose powder has improved flow property and compressibility than MCC by using this process

Importance of PS and PSD

1. Particle size affects many physical properties of drug like surface area, density, porosity, compressibility, and moisture absorption, surface properties like solubility, absorption, dissolution and bioavailability. 

2. Tablet: PS and PSD is important for selecting granulation process. It also affects average tablet weight variation, granules properties like uniformity of colour, size uniformity, also uniformity of dose, absorption, dissolution and finally bioavailability. 

3. Suspension: Sedimentation rate, suspendibility, redispersibility, coalescence and agglomeration.

4. Aerosol: Affects site of absorption in the bronchopulmonary tract.

5. Bioavailability: Drugs whose BA is increased by PS reduction are Sulphadiazine, Phenothiazen,                                       Tolbutamide, Spironolactone, Aspirin, Nitrofurantoin. 

• But in case of Nitrofurantoin, increase in bioavailability may result in increase in its side effects. 
• Penicillin-G and Erythromycin, if PS decreases, surface area increases; if remain more time in contact with GIF, so degradation increases. 
• Greseofulvin: If micronized the increases rate of absorption and finally the dissolution. 
• Poorly soluble hydrophobic drug: If PS decreases then there is increased chance of formation of agglomerates. 
• PS and PSD also affects the porosity and bulkiness so affects packing.

Compaction, Compression and Consolidation

Compaction:  

                       Compaction of powder is the term used to describe the situation in which materials are subjected to same level of mechanical force.

Compression: 

                       Compression is the reduction in the bulk volume of the material particle displacement of gaseous phase.

Consolidation:

                        Consolidation is the increase in mechanical strength of material resulting from particle–particle interactions.

Evalution of compaction

1. Strain index (SI): Measures internal strain associated with a powder when compacted. 

2. Bonding index (BI): Ability of material to the bonds. 

3. Brittle fracture index (BFI): Measures brittleness of material. Higher is the BI index, stronger is the        tablet. Higher is the SI index, softer is the tablet.

Effect of compaction on different factors

Compression force affects surface area, granule density, porosity and hardness and disintegration time of the pharmaceutical tablets.

• Surface area is increased to a maximum and then decreased. 
• The initial increase in surface area can be attributed to the formulation of new surface as the primary crystalline material is fragmented while the decrease in specific surface is due to cold bonding between the unit particles. 
•  Porosity is decreased and density is increased as a linear function of the logarithm of the compression force. 
• As the compression increases, the tablet hardness and fracture resistance also rises.

Moisture and compression

• Moisture is essential for the formation of the tablet.
•  Moisture increases the tensile strength of the tablet by increasing contact area for bonding 
• Moisture decreases particle surface energy and thus decreases adhesion of the tablet to the die wall.
•  In case of MCC, the moisture present within the pores facilitated the flow during the compaction.
•  Lack of moisture leads to lamination because of elastic recovery. 
• Excessive moisture produces capillary state of powder aggregation and thus surface tension effects are insignificant to have better compaction.

Sieve

A sieve consists of a pan with a bottom of wire cloth with square opening. In the US, two standards of sieve are used.

1. Tyler Standard scale–Ratio of the width of opening in successive sieves is 21/2. Tyler scale is based on size ofopening in a wire cloth having 200 openings per linear inch i.e., 200-mesh.

2. National Bureau of Standard also uses the ratio 21/2 but it is based on an opening of 1 mm (18 mesh).

Special terminology used in powder mixing 

1. Trituration:

                       Reducing the particle size by rubbing them in pestle– mortar.

2. Pulverization by intervention:

                                                       Powder is mixed with volatile solvent that can be easily removed after size reduction. 

                                                   Example–Camphor plus alcohol

3. Levigation:

                        Powder is mixed with a non-solvent and a paste is prepared, then it is rubbed to reduce the size. This method is particularly used when solute is incorporated into dermatological preparations. Mostly used non-solvent is mineral oil. 

4. Geometric dilution:

                                     It is used when potent substances must be mixed with a large amount of diluents.

(a) First, a potent drug and an approximately equal volume of diluents are placed in mortar and thoroughly mixed by trituration. 

(b) A second portion of diluents, equal in volume to the powder mixture in the mortar, is added and trituration is repeated. The process is continued; equal volume of  diluents are added to the powder mixture in the mortar until all of the diluents are incorporated.

5. Hygroscopicity

• Hygroscopicity: It is the tendency of material to absorb moisture from atmosphere and be in dynamic equilibrium with water in the atmosphere. 
•  Deliquescent: It is the hygroscopic substance which absorbs moisture from air to the extent that they liquefy by partially or wholly forming solution. 
• Efflorescent: A substance which loses water to form a lower hydrate or becomes anhydrous is termed as efflorescent.

Examples:

Glycerinated gelatin and PEG base of suppository are hygroscopic in nature.

• Moisture content can be determined by Thermo gravimetric analysis or by Karl Fisher titration or by gas chromatography