CAPSULESPresented by: K. Anupama M.Pharm [Q.A] 1st semester Guided by: Mr. R.P.Singh Asst. Professor PPD
What are CAPSULES ? Capsules are the solid dosage forms in which medicinal agents and/ or inert substances are enclosed in a small shell of gelatin. Capsule shells are made up of GELATIN based on which they are divided into 2 following types: 1. Hard Gelatin Capsules 2. Soft Gelatin Capsules
GELATIN Gelatin or semi solid protein is a transparent protein material that is obtained by the partial hydrolysis of collagen from skin, white connective tissue and bones of animals. Being a protein, it is digested by Proteolytic enzymes and is absorbed.
Bloom Strength Bloom is a test to measure the strength of a gel or gelatin. The test was originally developed and patented in 1925 by O. T. Bloom. The test determines the weight (in grams) needed by a probe (normally with a diameter of 0.5 inch) to deflect the surface of the gel 4 mm without breaking it. The result is expressed in Bloom (grades). It is usually between 30 and 300 Bloom. This method is most often used on soft gels. To perform the Bloom test on gelatin, a 6.67% gelatin solution is kept for 17-18 hours at 10C prior to being tested.
HARD GELATIN CAPSULES
SOFT GELATIN CAPSULES
ADVANTAGES OF CAPSULES AS DOSAGE FORMS Hard-gelatin capsules suitable for extemporaneous compounding so that the dose and combination of ingredients may vary depending on the patient's needs More stable than liquid dosage forms Small-particle size so that the dissolution and absorption in body fluids faster than pills and tablets Can cover up the taste and smell unpleasant medicine Liquid preparations can be made with a certain concentration. Can be used for depot capsules and enteric coated capsule.
DISADVANTAGES OF CAPSULES Hygroscopic drugs can not be filled in the capsule shells. The concentrated solutions which require previous dilution are unsuitable for capsules because if administered as such lead to irritation in stomach. Can not be used for materials that are very efflorescent or deliquescent. Efflorescent material make capsule become soft while deliquescent material causing the capsule to become brittle and easily broken. The bitter-medicine will cause vomiting and corrosive which are difficult to overcome. It take a relatively long compounding.
Hard Gelatin Capsule It is also referred as the dry filled capsule (D.F.C) because in this type of capsule, the shell is hard and consists of two sections used for filling dry materials in body capsule. Parts of a Hard gelatin capsule: 1. The Capsule Body 2. The Capsule Cap The two parts overlap when joined with the capsule fitting snugly over the open end of the capsule base.
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Composition Of Hard Gelatin Capsules A typical Hard gelatin capsule consists of the following materials: Gelatin Sugar Water Color with F.D & C, D&C dyes It is made opaque by adding Titanium dioxide
Moisture content Normally, hard gelatin capsule contain 1316 % of moisture.
Process of preparation of filled Hard gelatin capsules The large or small scale preparation of hard gelatin capsules is divided into the following general steps: 1. Developing and preparing the formulation and selecting the capsule size. 2. Filling the capsule shells. 3. Capsule sealing (optional). 4. Cleaning and polishing the filled capsule. 5. Filling tablets or small capsules into the capsules is sometimes useful in commercial production of capsules.
Filling of Hard gelatin capsulesPUNCH METHOD: Pharmacists may use punch method wherein the pharmacists take the precise number of empty capsules to be filled from the bulk container. Pharmacist guard against filling the wrong number of capsules and avoid contaminating the stock container with drug powder. The powder to be encapsulated is placed on a clean sheet of paper /glass/porcelain plate. Use spatula to mix the powder. Empty capsule is held between thumb and forefinger and punched vertically into the powder cake repeatedly until filled. Weigh the product after capping.
Hand Operated Capsule Filling Machine
They have capacities ranging from 24 to 300 capsules and when efficiently operated are capable of producing about 200-2000//hr.
Automated capsule filling machines
Capsule Sealing Hard Capsules may be sealed through: 1. Gelatin-band 2. Heat welding process 3. Thermal band
Note: Industrial Capsule sealing machines are capable of producing 60,000-150000 gelatin banded, heat welded, or thermally coupled capsule per hour.
Cleaning and Polishing ACCELA-COTA Apparatus is used to clean and polish the hard gelatin filled capsules.
Capsule Sizes For human use, the empty capsules ranging in size from 000 (Iargest) to 5 (smallest) are available. Larger capsules are used for veterinary use. The aim in developing the formulation and selecting the capsule size is : To prepare a capsule with : - accurate dosage, - good bioavailability, - ease of filling & production, - stability and - elegance
Stability of Hard Gelatin Capsule If hard gelatin capsules are stored in an environment of high humidity, additional moisture is absorbed by the capsules and they may become distorted and loose their rigid shape. If capsules are stored in extreme dry conditions, then some of the moisture normally present is lost and the capsule may become brittle and crumble. Moisture may be absorbed by gelatin capsule and affect hygroscopic agents present in capsule. That is why they are packed with small packets of dessicant materials (e.g. dried silica gel, clay, activated charcoal).
SOFT GELATIN CAPSULES These capsules are made of gelatin to which glycerine or a polyhydric alcohol such as sorbitol has been added to render the gelatin elastic or plastic like. Soft gelatin capsules consist of a filling, containing the dissolved or suspected active substance, and of a onepiece shell.
Properties of Soft Gelatin Capsules: It contains more moisture than hard gelatin capsules. May be manufactured to be oblong, oval, or round in shape. Add preservatives to retard microbial growth. They may be prepared from a single or double tone color and may be imprinted with identifying markings. They may be prepared with opaquants to reduce transparency and render characteristic feature to the capsule shell. Use hermetic (snug) seal. These capsules are pharmaceutically elegant & easily swallowed by the patient. These capsules can encapsulate liquids, suspensions, pasty materials, dry powders & even preformed tablets.
Base Adsorption Base adsorption is expressed as the number of grams of liquid base required to produce a capsulatable mixture when mixed with one gram of solid(s). The base adsorption of a solid is influenced by such factors such as the solids particle size and shape, its physical state (fibrous, amorphous, or crystalline), its density, its moisture content, and its oleophilic or hydrophilic nature. A practical procedure for determining base adsorption and for judging the adequate fluidity of a mixture is as follows:
Weigh a define amount of the solid (40g is convenient) into a 150 ml teared beaker. In a separate 150 ml beaker tared beaker, place about 100 g of the solid base. Add small increments of the liquid base to the solid, and using a spatula, stir the base into the solid after each addition until the solid is thoroughly wetted and uniformly coated with the base. This should produce a mixture that has a soft ointment like consistency. Continue to add liquid and stir until the mixture flows steadily from the spatula blade when held at a 45degree angle above the mixture. The base adsorption is obtained by means of the following formula Weight of the base/ Weight of the solid = Base Adsorption
Minim per gram factor The base adsorption is used to determine the minim per gram factor (M/g) of the solid(s). The minim per gram factor is the volume in minims that is occupied by one gram (S) of the solid plus the weight of the liquid base (BA) required to make a capsulatable mixture. It is calculated by dividing the weight of the base plus the gram of solid base (BA+ S) by the weight of the mixture (W) per cubic centimeter or 16.23 minims (V). A convenient formula is(BA + S) x V/ W = M/g Thus lower the base adsorption of the solid (s) and higher the density of the mixture, the smaller the capsule will be.
Composition of a Soft Gelatin Capsule Gelatin Softener (plasticizer): sorbitol, xylose, glycerine, PEG, Water. Preservatives: Methyl paraben, Propyl paraben, Butylated hydroxy aniline, EDTA, Sodium benzoate. Dyes. Solvents; Polar: glycerine, PEG, PEG 400, PEG 3350, Ethanol, PPG, Water. Non Polar: beeswax, coconut oil, triglycerine, corn oil, mineral oil, soyabean oil, D,L- Tocopherol. pH adjusting additive. Flavour and fragrance Pigment: titanium oxide, ferric oxide Anti-caking agent: Silicon dioxide Humectant: Polyol
Preparation of Soft Gelatin Capsules1. Plate Process: Using a set of moulds to form the capsules. 2. Rotating Die Process: Two continuous gelatin ribbons are brought together between twin rotating dies. This is the most common process in preparing soft gelatin capsule in industry. 3. Reciprocating die process: It is similar to the above process except that it uses reciprocating dies instead of rotary dies.
Rotary die Process
Reciprocating capsule filling machine
Advantages of Soft gelatin capsules: Ease of swallowing. Dosage accuracy/ uniformity. Consistent manufacturing requirements. Increase in bioavailability Enhanced stability and security Pliable shell Portability
QUALITY CONTROL PARAMETERS The Quality Control Tests that are performed for capsules are categorized as follows: 1. Physical tests 2. Chemical tests PHYSICAL TESTS include: a. Disintegration test b. Weight variation test CHEMICAL TESTS include: a. Dissolution b. Assay c. Content uniformity d. Stability testing e. Moisture permeation test
Physical Tests Disintegration Test: This test helps to determine whether the capsules disintegrate within the prescribed time when placed in a liquid medium under the prescribed experimental conditions. Weight variations Test: This demonstrates the uniformity of dosage units.
Chemical tests Dissolution Test: It determines the amount of drug substance that goes into the solution per unit time under standardized conditions of liquid/ solid interphase, temperature and solvent composition. This test is used in the pharmaceutical industry for optimization of formulation and quality control. Dissolution tests include: - In-vitro (in artificial environment) - In-vivo ( inside living organism)
Assay It refers to the determination of amount of specific substance in a drug mixture. It reflects the main active contents in a production batch.
Content uniformity It refers to the assay of the individual unit (i.e. capsules, tablets injections). It shows the distribution of active contents within the production batch.
Stability testing To determine the intrinsic stability of the active drug molecule and the influence of environmental factors such as temperature, humidity, light, formulative components and the container and closure system.
Moisture Permeation Test: To determine the degree and rate of moisture penetration by packaging the dosage unit together with a color revealing dessicant pellet and exposing the packaged unit to known relative humidity over a specified time. Then observing the dessicant pellet for color change and comparing the pre-test and post-test weight of the packaged unit.
References: http://nsdl.niscair.res.in/bitstream/123456789/747/1/Revised+ CAPSULES.pdf http://www.authorstream.com/Presentation/ackosisteph1111270-capsule-soft-gelatin/ http://en.wikipedia.org/wiki
