Capsules Flashcards
What are shells formed by?
Gelatine
What are capsules?
Solid dosage forms where the drug substance is enclosed within either a hard or a soft soluble shell
What are the majority of capsules produced today?
Hard gelatin capsules
What are antaacids?
For neutralisation of excess stomach acid associated indigestion. It also helps to protect the lining of your stomach from acid irritation.
Name a antaacid?
Aluminium hydroxide
What capsules are laxatives?
Typically soft gelatine capsules
What are loperamide for?
Acute diarrhoea
What are ACE inhibitors?
ACE inhibitors are medicines that aRe used mainly in the treatment of hypertension and heart failure
Name some ACE inhibitors?
Ramipril, Trandolapril
What are Beta-adrenoceptor blockers?
Are medicines that are used to treat a number of conditions including angina,high blood pressure,heart failure,heart attack, glaucoma and anxiety
Give examples of beta-adrenocepter blockers?
Propranolol, bedranol- modified release capsules or hard gelatin capsules
What are the two stages of hard gelatin capsules?
1 stage: shell manufacturing
2 stage: separate filling procedure
What are soft gelatin capsules filled with?
Solutions / suspensions of drugs in liquids that will NOT solubilise the shell
What are hard gelatin capsules filled with?
Powders, granules, pellets
What shape are hard gelatin capsules?
Typically oblong
What shape are soft gelatin capsules?
Spherical, oblong, oval , tube, suppository types
What is the size range of soft gelatin capsules?
1-480 minims (16.2 minim = 1L)
How many sizes of hard gelatin capsules?
8 ranging from volumetric capacity between 0.13-1.37 mL
What is the aim of soft gelatin capsules?
To mask the taste of certain unpleasant tasting medication (copaiba balsam)
What percentage of water is used for starch capsules?
13-14%
What temperature is used for starch capsules?
140-190 oC
What is HPMC?
A non gelatin capsule
What five things does the shell of a hard gelatin capsule contain?
Gelatin Colorants Opaquing agents Preservatives Water
How is gelatin produced?
By hydrolysis of collagen taken from animal connective tissue,bone,skin and sinew
What is gelatin?
Is a long polypeptide chain which yields 18 amino acids upon hydrolysis with most prevalent: Gly and Ala
What are the two types of gelatin?
Type A and B
What is type A gelatin produced by?
Acid hydrolysis
What is type B produced by?
Alkaline hydrolysis
What is type A mainly manufactured from?
Pork skin
What is type B mainly manufactured by?
Animal bones
What is the isoelectric point of type A?
7.0-9.0
What is the isoelectric point of type B?
4.8-5.0
What does type A provide?
Plasticity and clarity
What does type B provide?
Firmness
What range of weight of capsules is bloom strength suitable for?
150g-280g
What is the range of capsules suitable for viscosity?
30-60 millipoise
What do colorants do?
Easily identify product and improve patient compliance
What are opaquing agents?
Substances that protect the drugs from the light or to conceal the contents.
What substances is commonly used for opaquing agent?
Titanium dioxide (TiO2)
What is water used for?
For the dipping method and to adjust the viscosity
What % of gelatin solution is prepared in large stainless steel tanks?
30-40%
Whay is a vacuum applied to the gelatin viscous solution?
To remove entrapped air
What is the capsule moisture content?
13-16%
What are some problems of capsules relevant to appearance?
Small bubbles
Specks in the films
Marks in the cut edge
What is some problems of capsules on usage?
Splits
Long bodies
Grease inside
What is some problems with capsules from block filling machines?
Dented capsules
Imperfect cuts
Capsules with holes
How many sizes are capsules manufactured in?
8
What is the size range for gelatin capsules?
000-5
What is the largest size acceptable to patients?
No. 0 size and 00 having an elongated body
What are the sizes used for veterinary used and there respective capacities?
Sizes with No. 10,11,12 with capacities of 30,15,7.5g
What does a moisture content of <12% mean?
Brittle shells/ capsules
What does a moisture content of >18% mean?
Softened shells/ capsules
What relative humidity should be maintained during handling and storing?
40-60%
What does removal of humidity from the shell result in?
Splitting/cracking
What does transfer of moisture towards the content result in?
Caking of the drug from the powder
What would cause failure of the USP standards? And what causes this?
Loss of water solubility of the shell due to exposure to high humidity and temperature or traces of reactive aldehydes. Could be due to gelatin-cross linkage
What is capsule weight variation depends on?
Machine speed, specific volume,flowability, presence of glidant
What is capsule weight independent of?
Capsule size
What does a high CI% mean?
Indicates dominant cohesive and frictional interactions between the powder particulates. So it did related to the flowability of the powder used
What are lubricant crucial for?
To prevent filming in pistons and to reduce friction between the components and the powder and to facilitate the plug ejection
What is the Carr Compressibility Index?
Is calculated firm the loose and tapped bulk density according the equation
What are the powder requirements?
Fluidity
Compatibility
Lubricity
Moderate bulk density
What are some other materials other than powders?
Breads, pellets, microtablets, tablets and pasty and liquid material
What does drug release from the shell depend on?
Wearability of the powder mass
Rate that dissolution fluid penetrates the powder
Rate of disintegration and de-aggregation of the contents
Nature of the primary drug particles
What is the filling blend for hard gelatin capsules?
Active ingredient Fillers Glidant said Lubricants Disintegrants Surfactants
What is the dose solubility volume?
It’s the volume required to dissolve the dose kg the drug
What is the high solubility of the active ingredients?
Does soluble in 250ml or less water (volume of gastric fluid)
What is low solubility?
Dose soluble in more than 250ml of water at 37oC
What is the jejunal permeability?
2-4x10-4
Do class I drugs have high or low solubility?
High solubility and permeability
What is the advantage of micronisation?
Increase the surface area and enhance water solubility
What is the limitations of micronisation?
High surface/mass ratio which leads to particle aggregation (cohesive interaction) which reduces the surface area for dissolution
Why do large particle exhibit poorer flow conspiring to larger particles? And how can this be resolved?
Due to cohesive and frictional interactions this can be resolved by granulation
What are fillers (diluents)?
Increase the bulk of the formulation and can provide cohesion to the powder
What are commonly used fillers?
Lactose,microcrystalline cellulose and starch. Also inorganic salts
What should fillers have?
A small particle size
What do modified fillers offer?
Better compatibility and flowability
What do glidants do?
They improve the flow properties of the powder mix or granules. They are finely divided dry powders added to formulations in small quantities as they are absorbed into the surfaces of the bulk powder particles
What are the mechanisms of glidants?
They decrease the roughness by filling surface irregularities
They decrease attractive forces by separating bulk powder particles
They modify electrostatic charges
They act as moisture scavengers
They serve as ball bearing between bulk powder particles
Name some commonly used glidants?
Colloidal silicas, cornstarch, talc, magnesium stearate
What do lubricants do?
Ease the ejection of plugs
Reduce filming on pistons and adhesion of powder to metal surfaces
Reduce friction between sliding surface in contact with powder
What is the problem with high concentrated hydrophobic lubricants?
Causes drug deformities
What makes a lubricant effective?
Hydrophobic stearates
Name some lubricants?
Magnesium stearate, calcium stearate, stearic acid
Less effective lubricants are less hydrophobic , give some examples?
Hydrogenated vegetable oils , PEG, sodium stearate fumarate
What do surfactant do?
Increase the wetting of the powder made and enhance drug dissolution
What can surfactants compensate for?
The problem created due to the presence of the lubricant
Name some common surfactants
Sodium lauryl sulphate, sodium docusate at levels 0.1-0.5%
What does hydrophilization and granulation aim to do?
Improve sett ability of poorly soluble drugs using hydrophilic polymers
What is hydrophilization?
Mixing drug with an hydrophilic polymer in a dry state and using a high sheer mixer
What could wet granulation using a binder such as PVP do?
Improve the solubility of the drug
What does granulation do?
Reduce the bulk volume, enhances flow properties, reduce agglomeration of fine particles or their adhesion to mental surfaces and improve the content uniformity of low-dose drugs
What is the drawback of granulation? So what is used?
Sensitive drugs to moisture and temperature. Dry granulation or non-aqueous solvent is used
What are some advantages of soft gelatin capsules?
High reproducibility , High bioavailability, hermetically sealed due to manufacturing procedure so is suitable for liquids and volatile drugs and drugs vulnerable to atmospheric drugs, wide variety of sizes and shapes
What are disadvantages of soft gelatin capsules?
Additional quality controls are required, possible interaction between liquid and the soft gelatin shell which could lead to gelatin hydrolysis
What are the basic components of a soft gelatin capsule shell?
Gelatin Plasticizer: gelatin, sorbitol, propylene glycol Dyes Opacifiers Preservatives Flavors
What sit he aim of soft gelatin capsules?
To produce the smallest possible capsule consistent with maximum stability, therapeutic effectiveness, manufacture efficiency
What can the liquid form be in soft gelatin capsules?
Single liquids
Combination of miscible liquids
Solution or suspension of a drug in liquids
What does the pH range for a soft gelatin capsule have to be?
Liquids pH: 2.5-7.5
What happens if Ph is <2.5?
Leakage due to gelatin hydrolysis
What happens if pH is >7.5?
Gelatin solubility reduction due to polymerisation
Why can’t aqueous emulsions be filled?
Water will be released resulting in leakage
Name a hydrophilic liquids used?
PEG 400
Name a lipophilic liquid?
Triglyceride oil
What are not allowed for a filling liquid?
> 5% water and small alcohols
Name a vehicle used for filling liquids
PEG 400 a water-miscible non-volatile liquids
What temperature requirement must liquids have?
Gravity at 35oC or less
What must the sealing temperature of gelatin films be?
37-40oC
What are suspending agents for oily bases?
Beeswax (5%) Paraffin wax (5%) Animal stearates (1-6%)
What are some suspending agents for non-oily bases?
PEG 400, PEG 600 (1-5%)
Solid non-ionics (10%)
Solid glycol esters (10%)
What must a container dispensing capsules be?
Tight,well-closed and light resistant
How do you work out the % of dose in a capsule?
Divide the dose in mg by the total weight of the capsule in mg then x 100
