TABLETS AND SUPPOSITORIES Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics Faculty of Pharmacy Omer Al-Mukhtar University Tobruk,

TABLETS AND SUPPOSITORIES

Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D

Department of PharmaceuticsFaculty of Pharmacy

Omer Al-Mukhtar UniversityTobruk, Libya.

E-mail: [email protected]

2014/06/17 1Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

CONTENTSTablets

• Introduction (properties of tablet granulation)

• Tablet additives and components

• Disintegrant

• Colorant

• Flavor and sweeteners

• Preparation of components for compression

• Forms of compressed tablets

• Processing problems

• Evaluation of tablets

• Tablet coating (sugar coat, film coat)

2014/06/17 2Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Introduction (Properties of Tablet Granulation)

• Granulation is the process in which primary powder particles are made to adhere to form larger multi-particle entities called granules.

• Granulation normally commences after initial dry mixing of the necessary powdered ingredients so that a uniform distribution of each ingredient through the mix is achieved.

• After granulation, the granules will either be packed (when used as a dosage form) or they may be mixed with other excipients prior to tablet compaction.

2014/06/17 3Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Tablet additives and components

• A study of the physical properties of drug molecules is a prerequisite for product formulation and leads to a better understanding of the relationship between a drug’s molecular and physicochemcial properties and its structure and action.

• These properties come from the molecular bonding order of the atoms in the molecule and may be though of as either additive or constitutive (dependent on the structural arrangement of the atoms within the molecule).

2014/06/17 4Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Disintegrant

• The substance which are added in the tablet formulation to ensure disintegration of the tablets into smaller particles when swallowed are called Disintegrant or Disintegrating Agents.

• These are added into the formulation of or oral tablets or sublingual tablets.

• When the medicament is insoluble in water a disintegrating agent is needed.

• Disintegrating agents act in three ways:

1. By swelling e.g. potato starch, maize starch, wheat starch.

2. By producing effervescence e.g. sodium bicarbonate

3. They melt at body temperature e.g. cocabutter

2014/06/17 5Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Colorant

• Colours of aproved certified F. D. and C, dyes are used.

• The colours are used to improve the elegance of the tablet.

• The colours are added to the solution of the granulating agent or these are mixed with other ingredients before granulation.

2014/06/17 6Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Flavours

• Flavours are included in lozenges, effervescent tablets and chewable tablets.

• Flavours are volatile oils and hence they are added into the granules just before compression of tablets.

• Flavouring agent is dissolved in organic solvent and the solution is sprayed on the granules.

2014/06/17 7Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Sweeteners

• Sweeteners are agents are used to improve the taste of tablets.

• These are used in lozenges and chewable tablets.

• Artificial sweetening agents like saccharin and cyclamates, are not used nowadays.

• Sucrose, lactose and mannitol are some of the commonly used sweetening agents.

2014/06/17 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya. 8

1. Weighing of the ingredients

2. Mixing the powdered ingredients and excipients

3. Converting the mixed ingredients into granules

4. Diluents

5. Granulating agents

6. Binding agents

7. Disintegrating agents

8. Lubricants

9. Adsorbents

10. Colouring agents, Flavouring agents and Sweetening agents.

2014/06/17 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya. 9

Preparation of components for compression

Forms of compressed tablets

• Tablets are prepared by the compression method and are hence called the “Compressed Tablets”

1. Multilayered tablets

2. Sustained action tablets

3. Enteric coated tablets

4. Sugar coated tablets

5. Film coated tablets

6. Chewable tablets

7. Buccal tablets Sublingual tablets

8. Lozenge tablets and traches

9. Dental cones

2014/06/17 10Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Processing problems

• The following defects may occur during the compression of granules into tablets.

1. Capping

2. Picking and sticking

3. Mottling

4. Weight variation

5. Hardness variation

6. Double impression

2014/06/17 11Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

• The following test should be carried to maintain the quality control of tablets:

1. Shape of tablets

2. Appearance

3. Content of active ingredient in tablets

4. Uniformity of weight

5. Disintegration test for tablets

6. Dissolution test for tablets

7. Mechanical strength

8. Friability test.

2014/06/17 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

12

Evaluation of tablets

Tablet coating (Sugar coat)

• Sugar coating is done by the pan coating method.

• It is one of the oldest arts to mask the unpleasant flavours and tastes of medicaments, but nowadays sugar coating of tablets is done for improving its aesthetic value.

• The various stages in the sugar coating process are:1. Sieving

2. Sealing

3. Subcoating

4. Syrup coating

5. Finishing

6. Polishing

2014/06/17 13Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

2014/06/17 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya. 14

Tablet coating (Sugar coat)

• In this case the tablets are coated by a single or mixture of film forming polymers, such as, hydroxypropyl methylcellulose, hydroxyethyl methyl cellulose, carbowax, polyethylen glycol 400 etc.

• The polymer is dissolved in some volatile organic solvent and is sprayed over the tablets in a rotating pan.

• The process is continued till a uniform good film is formed over the tablets.

• Film coating is also used to make the tablets water proof before the sugar coating.

• Film coating can be enteric or non-enteric2014/06/17 Faculty of Pharmacy, Omer Al-Mukhtar University,

Tobrum, Libya. 15

Tablet coating (Film coat)

CONTENTSSuppositories

• Introduction

• Advantages rectum physiology

• Drug absorption form rectum

• Factors affecting formulation of suppositories

• Classification of bases

• Choice of adjuvant

• Suppository production

• Quality control

• References2014/06/17 16Faculty of Pharmacy, Omer Al-Mukhtar University,

Tobrum, Libya.

Introduction1. The patient have a problem with their gastrointestinal tract, is

nauseous or is postoperative.

2. Several categories of patients, i.e. the very young, the very old or the mentally disturbed, may more easily use the rectal than the oral route.

3. The drug under consideration is less suited for oral administration.

4. The drug may be insufficiently stable at the pH of the GI tract, or susceptible to enzymatic attack in the GI tract or during the first passage of the liver after absorption.

5. The formulation into suppositories of certain drugs that are candidates for abuse, as in suicide, has also been considered.

2014/06/17 17Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Definition of Suppositories

• Suppositories are solid dosage form of medicament for insertion into body cavities other than mouth. They may be inserted into rectum, vagina or nasal cavity.

• The medicament is incorporated into the supository base and the product is formulated in such a way that they will either melt or dissolve in the body cavity fluid to release the medicament.

• Suppositories are available in different shapes, sizes and weights. Suppositories are used to produce local, systemic and mechanical action.

2014/06/17 18Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

• Under normal circumstances the rectum is empty; filling provokes a defection reflex, which is under voluntary control.

• Data comparing drug absorption from freshly prepared and aged, more viscous suppositories suggest that there is enough motility to provoke the spreading even of rather viscous suppositories.

• Suppositories are inserted in to rectum to promote evacuation of the bowel.

Advantages rectum physiology

2014/06/17 19Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Advantages of Suppositories

1. These can be easily administered to children, old persons and to unconscious patients who cannot swallow the drug easily.

2. These are inserted into body cavity to produce local effect of the medicament incorporated in the base.

3. These are inserted into the rectum to exert a direct and rapid action on the rectum.

4. These are inserted into the rectum to promote evacuation of the bowel.

5. Suppositories are unit dosage form of drugs2014/06/17 20Faculty of Pharmacy, Omer Al-Mukhtar University,

Tobrum, Libya.

Drug absorption form rectum

• Blood supply, especially venous drainage, is important for the understanding of drug absorption.

• Recent investigation have shown that avoiding the first passage through the liver is possible, but the extent of this effect cannot be generalized, as it will depend on the actual part of the rectum through which the drug is absorbed

2014/06/17 21Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Factors affecting formulation of suppositories

1. Drug solubility in vehicle: The drug solubility in the vehicle is of special interest from the biopharmaceutical point of view.

2. Surface properties: The surface properties of drug particles are also important as these particles will be transferred from one phase to another.

3. Particle size: The particle size of the drug is an important parameter, both technologically and biopharmaceutically.

4. Amount of drug: A complicating factor is the amount of drug present in a suppository. If the number of particles increases, this would also increase the rate to form agglomerates.

2014/06/17 22Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Classification of bases

• Suppository bases can be broadly classified into three categories:-

1. Fatty bases eg. Theobroma oil

2. Water soluble and water miscible bases eg. Glycero-gelatin

3. Emulsifying bases eg. Witepsol, massa estarinum, massuppol.

2014/06/17 23Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Choice of adjuvant

• Colloidal silicon oxide or aluminium monostearate, both approximately 1-2%

• The addition of lecithin is a worthy possibility when high amounts of solid drug are used.

• Surfactans act as wetting agents

• Surfactants may also act as ‘deglomerators’ which may prevent the formation of cake in the melting suppository, which in turn would certainly slow down the drug release.

2014/06/17 24Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Suppository production

• Suppositories are manufactured both on a small scale in batches of 10-20 and on a (semi) automatic scale in batches up to 20 000 per hour.

• Essentially the mode of manufacture is similar in both cases, and involves melting of the vehicle, mixing the drug and the molten vehicle, dispensing in a former cooling to solidify and, if necessary, packing in the final container.

• This includes a number of technological processes for which the relevant theory should be considered.

2014/06/17 25Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Suppository production

• The suppositories are prepared by any of the following methods:-

1. Rolling method

2. Hot process or fusion method

3. Cold compression method

2014/06/17 26Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

1. Rolling method: It is an ancient method of preparing the suppositories. The suppository base is rolled and then desired shape is given with the hand. The method is not used nowadays.

2. Hot process or fusion method: This method is commonly used in the preparation of suppositories for dispensing purposes. The suppository base is melted, the medicament is incorporated in it and filled in lubricated mould. On cooling, suppositories are formed which are removed from the suppository mould.

3. Cold compression method: The method is useful for thermolabile and insoluble drugs because heating and stirring of the base with medicament is not required.

Suppository production

2014/06/17 27Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

Quality control

• A list of properties that should be controlled.

1. Appearance (odour, colour, surface condition and shape)

2. Weight

3. Disintegration

4. Melting (dissolution) behaviour

5. Mechanical strength

6. Content of active ingredient

7. Release

2014/06/17 28Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.

THANK YOUe-mail: [email protected]

2014/06/17 29Faculty of Pharmacy, Omer Al-Mukhtar University, Tobrum, Libya.