Tablet:Ideal properties of API for formulating tablets
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High Purity
API has to be in pure form otherwise impurities can catalyze series of chemical reactions, e.g. in case of hydrocortisone impurity of cupric ion causes oxidation of ketone functional group. API should meet specifications given in the respective Pharmacopoeia.
High stability
The API should be stable against photolysis, oxidation, hydrolysis, etc. to keep the formulation a simple one. Sensitive particles require careful handling during manufacturing.
Good compatibility with excipients
(47)
In order to formulate a tablet one need to add excipient along with API. There should not be any kind of interaction between excipient and API. Excipients have to be inert in nature. However there are some reported examples of API-excipient interactions like Lisinopril reacts with lactose and undergoes browning reaction leading to darkening on storage. So, avoid the use of lactose and use other fillers for API containing primary amine. To ascertain drug and excipient interaction, 1:1 mixture is prepared and stored under accelerated/ICH conditions. The amount of drug degraded shall be determined to select the most suitable excipient.
Optimum bulk powder properties
Bulk powder properties have to be optimum to:
i) Prevent segregation.
ii) Have optimum size tablet particularly for low potency-low density API.
iii) Have good flow.
Optimum and Uniform particle size-particle size distribution
API should have uniform particle size and close particle size distribution because it has pronounce effect on uniformity of content, uniformity of weight, disintegration time, granule friability, drying rate kinetics of wet granulation, flowability, compressibility, stability, dissolution, bioavailability, etc. The flow and compression characteristics are important from the viewpoint of industrial pharmacist. Strong tablets are obtained if fine particles are used due to increase in surface area and surface energy.
Spherical shape
The shape of particles decides flowability. Spherical shaped particles exhibit good flow as compared to needle shaped particles. Particles with irregular shape may exhibit hindered flow due to interlocking between particles. This point is very important since it is directly related with weight of tablet and uniformity.
Good flowability
(48-50)
Flow is important for having uniformity of weight and uniformity of drug content. It can be measured using angle of repose, Carr’s index and Hausner ratio.
The methods used to improve flow are summarized below
i) Addition of glidants
ii) Addition of fines: Addition of fines up to certain extent improves flow. This is because of filling of void space and decrease in surface roughness.
iii) By wet granulation: Wet granulation gives regular sphere shaped granules and removes static charge if present on particle surface. Thus, flow property improved.
iv) By densification with help of slugging.
Optimum moisture content
(51-53)
Moisture content has to be optimum because of the following reasons:
i) Total lack of moisture results into brittle tablet.
ii) Moisture affects flow, which in turn affects uniformity of content.
iii) High amount of moisture gives stickiness, which will affect compaction. iv) Picking/sticking may be observed.
Moisture content can be controlled by:
i) Use of anhydrous salts.
ii) Use of non-aqueous solvent.
iii) Optimum drying time.
iv) Addition of finely powdered adsorbent like magnesium oxide.
Good compressibility
(1,2,4,5,54)
API should exhibit good compressibility. However this depends upon its intrinsic nature like:
(A)Elasticity:
The particles deform under the effect of pressure in a die but they revert back to original state on removal of applied pressure i.e. on ejection. Such tablets may exhibit capping and or lamination. The intrinsic nature of particle can be changed by:
i) Wet massing
ii) Pre-compression
iii) Plastic tabulating matrix (micro crystalline cellulose)Elastic material is less suitable for direct compression.
(B) Plasticity:
Plastic material gets bonded after viscoelastic deformation. Viscoelastic deformation is time dependent. Hence, the crushing
strength is dependent on the time that tablet spends in a die. Changing the turret speed can change dwell time. Plastic materials
may exhibit viscoelastic deformaiton.
(C)Brittle fracture:
A particle fractures into small particles on application of pressure in a die. Brittle fracture also promotes tableting. Brittle materials are less lubricant sensitive as compared to plastic materials. A blend of lactose and MCC is widely used in industry to get advantages of brittle materials and plastic materials.
Absence of static charge on surface
(55)
It is important because of the following reasons:
i) Affects uniformity of dose and weight variation (flow worsen if attractive forces generated).
ii) During mixing it may cause segregation and lead to non-uniformity of content if API and excipients are charged.
iii) Charged API may adhere to feed frame and result into serious damage to tablet equipment.
In order to remove charge certain treatments can be given like granulation, addition of diluents or lubricant, surface coating with help of colloidal silica, etc.
Good organoleptic properties
Many API are unpalatable and unattractive in their natural form. In such cases, tablet formulation require certain care. API has to be checked for colour and taste.
I. Colour
Ideally API should be colourless. For coloured API, the following steps shall be considered:
i) Select appropriate excipient to avoid mottling.
ii) Incorporate API in smallest particle size.
iii) Incorporate colour in dry form along with binder and activate mixture by addition of water or other activator.
iv) Coating can be applied to conceal non-uniform colour (sugar coated multivitamin tablet).
II. Taste
It is very important for tablets because they come in contact with taste buds. Ideally API should have no taste. But sometimes it might have unpleasant taste like bitter e.g. Chloramphenicol, Clindamycin, etc. The following taste masking options can be tried:
i) Use of prodrug to decrease API solubility in saliva or to reduce affinity for taste receptor e.g. Chloramphenicol Palmitate.
ii) Sugar coating or film coating.
iii) Addition of sweeteners like mannitol in cause of fast dissolving tablet or chewable tablet.
iv) Use of drug-ion exchange adsorbent in formulation.
v) Drug β-cyclodextrin complex may exhibit good taste profile and good compressibility as well.
Miscellaneous points
i) API should not exhibit sublime characteristics
ii) Liquid APIs are less suitable for tablet formulation. One of the options is conversion of liquid in pseudosolid (mix liquid API with adsorbents). A combination of Valproic acid and Sodium Valproate is a typical example of converting a liquid into pseudosolid.
iii) BCS class IV drugs are difficult to formulate if dissolution and bioavailability requirements are to meet as per regulatory agencies.
Key Phrases
- High Purity to avoid contamination and degradation.
- High stability against photolysis, oxidation, hydrolysis, etc.
- Good compatibility with excipients. For example, avoid use of lactose with drugs with primary amine functional group.
- Optimum bulk powder properties to prevent segregation and to have good flow.
- Optimum particle size and size distribution to have uniformity of weight, uniformity of content, good flow and compressibility.
- Spherical shape to avoid interlocking between the particles and thus to aid flow.
- Good flow to have uniformity of weight and uniformity of drug content.
- Optimum amount of moisture to avoid problems like brittle tablet, picking/sticking, etc.
- Good compressibility to have nicely bonded tablet.
- Absence of static charge on the surface to prevent demixing and damage to tableting equipment by adhering to feed frame.
- Good organoleptic properties to have better patient acceptance.
- Miscellaneous: Convert liquid API to pseudosolid e.g. Valproic acid and Sodium valproate, etc.
Next Page: Operations involved in tablet manufacturing
Previous Page: Formulation of
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