MANUF LAB CAPSULES

CAPSULE

Solid dosage forms in which one or more medicinal and inert ingredients are enclosed in a small shell or container.

Elegance; Ease of use; Portability; Smooth and slippery textures for ready swallowing; Capsules mask the taste and odor of unpleasant drugs and can be easily administered; Identifiable - such as color; Limited potential for incompatibilities; Good stability; Adaptability for individualized formulas and/or dosage

ADVANTAGES OF CAPSULE (9)

KCl, KBr, or NH4Cl,

[Limitations of Capsules as a Dosage Forms] Not usually used for the administration of extremely soluble salts, such as _____, ______, or _______ due to sudden release of the drug in the GIT, which may be irritating

Efflorescent materials

Give off water, which may cause softening of the capsule shells.

Deliquescent materials

Absorb water, and may dehydrate the capsule shells.

highly efflorescent or deliquescent materials

Capsules are not used for these two types of materials.

Mothes and Dublanc

[History of Capsules] Gelatin capsules were first prepared in France by ____________

1834

[History of Capsules] Capsules were first patented in __________

James Murdock; 1848

[History of Capsules] The two-piece telescoping hard gelatin capsule was invented by ______________ of London in year ___________

Hard Gelatin and Soft Gelatin Capsules

Types of capsules

Telescoping Capsules or Dry-Filled capsules

Other terms for hard gelatin capsule (2)

Body and cap

Two parts of hard gelatin capsule

Gelatin Blends, Certified Dyes, Opaquing Agents (Opaquants), Plasticizers, Preservatives, A Material such as Methyl cellulose, Polyvinyl alcohol, or denatured gelatin.

Materials for hard gelatin capsules (6)

Gelatin

A heterogeneous product derived by irreversible hydrolytic extraction of treated animal collagen

Pork skins, Pork and cattle bones, Split cattle hides

Gelatin can be made from ____________ (3)

Boiling

Gelatin is made through prolonged ___________ of animal skin, connective tissue or bones.

Pork Skin Gelatin and Calf Bone Gelatin

Two compositions of Gelatin Blends for Capsules

Pork Skin Gelatin

[Composition of gelatin blend for capsules] contributes to the plasticity and clarity, and reduces haze or cloudiness of the finished capsules

Contributes plasticity, clarity, and reduces haze

Function of pork skin gelatin

Calf Bone Gelatin

[Composition of gelatin blend for capsules] gives a tough, firm film but tends to be hazy and brittle by itself.

Hazy and brittle by itself

Limitations of calf bone gelation

Denatured gelatin

It modifies the solubility of capsules and produces an enteric effect

Methyl cellulose, Polyvinyl alcohol, Denatured gelatin

Other materials to be put in gelatin can be either these (3)

12-15%

The moisture content of Hard Gelatin Capsules should be between ________%

capsule softening or becoming brittle.

This degree of hydration (12-15% moisture) should be maintained to avoid capsule __________ or becoming ___________

Hydroxypropyl methylcellulose (HPMC)

Hypromellose other name

Hypromellose

Alternative to gelatin in capsule shell production

plasticizer and water

Hard capsules are usually made up of a base containing ________ and ________

000

[Size of Capsule accdng to approx. capacity] 950 mg

00

[Size of Capsule accdng to approx. capacity] 650

0

[Size of Capsule accdng to approx. capacity] 450

1

[Size of Capsule accdng to approx. capacity] 300

2

[Size of Capsule accdng to approx. capacity] 250

3

[Size of Capsule accdng to approx. capacity] 200

4

[Size of Capsule accdng to approx. capacity] 150

5

[Size of Capsule accdng to approx. capacity] 100

Preparation, Dipping, Spinning, Drying, Stripping, Trimming and Joining, Polishing

Steps in Making Hard Gel Capsules (7)

gelatin and hot demineralized water

[Preparation] Once starting materials have been received and released by Quality Control, the ___________ and ____________are mixed under vacuum in the Stainless Steel Gelatin Melting System.

feed tanks

[Preparation] After aging in stainless steel receiving tanks, the gelatin solution is transferred to stainless steel ___________

Dyes, opaquants, and any needed water

[Preparation] _________, __________, and any needed ___________ are added to the gelatin in the feed tanks to complete the gelatin preparation procedure. The feed tanks are then used to gravity-feed gelatin into the Capsule Machine.

Dipper

[Dipping] From the feed tank, the gelatin is gravity fed to specially engineered ___________ section.

Pin Bars

[Dipping] Here, the capsules are molded onto stainless steel ____________ which are dipped into the gelatin solution.

50°C

[Dipping] The dipping solution is maintained at a temperature of about __________ in a heated, jacketed dipping pan

Spinning

[Steps in making Hard Gel Capsules] Once dipped, the Pin Bars rise to the upper deck allowing the cap and body to set on the Pins. The pins are rotated to distribute the gelatin over the pins uniformly and to avoid the formation of a bead at the capsule ends.

Drying

[Steps in making Hard Gel Capsules] Pin Bars pass through the upper and lower kilns of the Capsule Machine Drying System.

volume, temperature, and humidity

[Drying] Here gently moving air which is precisely controlled for_________, __________, and ____________, removes the exact amount of moisture from the capsule halves

Stripping

[Steps in making Hard Gel Capsules] Once drying is complete, the Pin Bars enter the Table section which positions the capsule halves for _____________ from the Pins in the Automatic section

stationary knives

[Trimming and Joining] The stripped cap and body portions are trimmed to the required length by ________________

Joined

[Trimming and Joining] After trimming to the right length, the cap and body portion are __________ and ejected from the machine.

Polishing

[Steps in making Hard Gel Capsules] Finished capsules are pushed onto a conveyer belt which carries them out to a container

Polishing

[Steps in making Hard Gel Capsules] Perfect capsules are imprinted with the client logo on high- speed capsule printing machines. Capsules are now ready to be sterilized and packaged.

Powders, Pellets, Granules, Tablets

Fill Materials: Dry Solids (4)

Suspensions, Pastes

Fill Materials: Semisolids (2)

Non-aqueous liquids

Fill Materials: Liquids

Hygroscopic drug

[Difficulties in HGC Filling] A gelatin capsule contain water which is extracted or taken up by a __________ drug and renders the capsule very brittle which leads to cracking of the capsule

magnesium carbonate, heavy magnesium oxide or light magnesium oxide

[Difficulties in HGC Filling] Adsorbents used for HGC filling (3)

vials

[Difficulties in HGC Filling] The addition of an adsorbent overcomes the difficulty posed by deliquescent or hygroscopic powders provided the capsules are packed in tightly closed glass capsule _______

Eutectic Mixtures

[Difficulties in HGC Filling] Certain substances when mixed together tend to liquefy and form a pasty mass due to the formation of a mixture which has a lower melting point than room temperature

Absorbent

[Difficulties in HGC Filling] For filling these types of substances (eutectic mixtures) each troublesome ingredient is mixed with an _____________ separately then mixed together and filled in capsules.

Magnesium oxide and Kaolin

[Difficulties in HGC Filling] Absorbents used in preventing in remedying eutectic mixtures (2)

magnesium carbonate or kaolin

[Difficulties in HGC Filling] Another method in dealing with eutectic mixtures is that the substances are mixed together so as to form a eutectic mixture, then an absorbent like _____________ or _____________ is added.

Diluent

[Difficulties in HGC Filling] Incompatible Ingredients - When the quantity of the drug to be filled in capsules is very small and it is not possible to fill this much small amount in capsules then inert substance or a ____________ is added so as to increase the bulk of the powder, which can be filled easily in capsules.

Very Small Drug Quantity

[Difficulties in HGC Filling] Some of the manufacturers separate the incompatible ingredients of the formulation by placing one of the ingredients in smaller capsule, and then placing this smaller capsule in a larger capsule containing the other ingredients of the formulation

Adhesiveness

[Difficulties in HGC Filling] Filling of Granular Powder - Some powders which lack _______________ and most granular powders are difficult to fill in the capsules by punch method because they are not compressible and flow out of the capsule as soon as they are lifted from the pile of powder into which they are punched.

Moistened with alcohol; reduced to powder

[Difficulties in HGC Filling] To overcome this difficulty (filling of granular powder) the non-adhesive powders should be moistened with ___________ and the granular powders should be reduced to ___________ before filling into capsules

Deliquescent or Hygroscopic powders; Eutectic Mixtures; Incompatible Ingredients; Very Small Drug Quantity; Filling of Granular Powder

Difficulties in Filling of HGCs (5)

100 deg F

[Proper storage of empty HGC] Temperature of storage should not exceed ____________

12-15%

[Proper storage of empty HGC] Empty gelatin capsules contain _____________% moisture.

Below 10%

[Proper storage of empty HGC] If the moisture content of the HGC is below _____% the capsules become brittle and may shrink (to the point of not fitting in the filling equipment.)

Distortion

[Proper storage of empty HGC] Exposure to either heat or excessive moisture should be avoided, as it could cause the _________ of the capsule shells.

soft and tacky

At high moisture levels, capsules absorb moisture, eventually becoming ___________ and ____________

Become brittle; suffer dimensional changes

At low moisture levels, capsules shells become ___________ and suffer _________________, causing handling problems in the filling machines.

Salt Polishing

[Finishing Hard Gelatin Capsule] With this procedure, the filled capsules are rotated in a polishing pan, along with granular sodium chloride.

Granular sodium chloride

[Finishing Hard Gelatin Capsule] Salt used in salt polishing

Salt Polishing

[Finishing Hard Gelatin Capsule] Certain hygroscopic materials (such as vitamins or granular materials) are not readily removed from capsules by this technique.

Salt Polishing

[Finishing Hard Gelatin Capsule] This method may damage capsules that have been imprinted "prior" to filling.

Type and particle size

[Finishing Hard Gelatin Capsule] In salt polishing, the _____________ and ____________ of the salt requires individual experimentation.

Pan Polishing

[Finishing Hard Gelatin Capsule] The tablet coating pan may be used to dust and polish the capsules.

polyurethane or cheese cloth line

[Finishing Hard Gelatin Capsule] A _________ or ______________ is placed in the pan and the liner is used to trap the removed dust as well as to impart gloss to the capsules.

Cloth dusting

[Finishing Hard Gelatin Capsule] This is a hand-operated procedure where the bulk filled capsules are rubbed with a cloth (may or may not be impregnated with oil). It imparts an improved gloss to the capsules.

Brushing

[Finishing Hard Gelatin Capsule] The capsules are fed under rotating soft brushes, which remove the dust from the capsules shells.

Vacuum

[Finishing Hard Gelatin Capsule] A ___________ for dust removal must accompany this "Brushing" operation.

Brushing

[Finishing Hard Gelatin Capsule] In this method, some materials are difficult to remove to the point of deformation of the capsules. (by scratching the surface of the shell). Also, no commercial equipment available for this method.

Salt polishing, Pan polishing, Cloth Dusting, Brushing

Methods of finishing Hard Gel Capsules (4)

Imprinting

[Special Techniques for HGCs] A convenient method for product identification and control; It is best performed on empty capsules;

edible inks

[Special Techniques for HGCs] What kind of inks are used for imprinting.

Provide a DISTINCTIVE APPEARANCE to the product. b. PREVENT filled capsules from UNJOINING. c. permit COLOR CODING. d. provide a TAMPER-PROOF FEATURE to each individual capsule.

[Special Techniques for HGCs] Functions Sealing and/or Banding Operations

Locking Capsules

[Special Techniques for HGCs] Deliberate modification is made on one or more of the normal contours of the capsules so that the body is more tightly held, in relation to the cap after closing

Special Purpose Capsules

[Special Techniques for HGCs] It refers to special capsules to which a special treatment has been given to retard the solubility;

Delay absorption; provide enteric properties

[Special Techniques for HGCs] Special purpose capsules are done to delay _____________ of a certain ingredient or to provide ___________ properties

Imprinting, Sealing and/or Banding Operations, Locking Capsules, Special Purpose Capsules

Special techniques for HGCs (4)

Pearls

Soft Gelatin Capsules are also known as ________________

Gelatin

Soft Gelatin Capsules are made from shells of _______________

Glycerin or a polyhydric alcohol (such as sorbitol)

SGCs are made of gelatin to which ___________ or a _____________ has been added.

liquids, suspensions, pasty materials, dry powders, and even preformed tablets.

Soft gelatin capsules are used to encapsulate and hermetically seal _________________ (5)

As an oral dosage form for Human or Veterinary Use; As a suppository for rectal or vaginal use; As a special package in tube form for topical application; and in the cosmetic industry

Pharmaceutical applications of soft gelatin capsules (4)

Gelatin, Plasticizers, Water, Optional Components

Materials for Soft Gelatin Capsules (4)

Preservatives, colorants, opacifying agents, flavoring agents

Optional components for Soft Gelatin Capsules (4)

bloom or gel strength, viscosity, and iron content

[Materials for Soft Gelatin Capsules] USP capsules made from Gelatin come with additional specifications such as ________________ (3)

Gelatin, plasticizers, materials for appearance, flavors

[Materials for Soft Gelatin Capsules] Typical soft gels are made up of _________, ____________, and materials that impart the desired _____________ (colorants and/or opacifiers), and sometimes ______________.