Tablet Formulation Lecture 2 PDF

LECTURE 2 TABLET (1)  2  Tablets  Solid dosage form comprises tablets and capsules constitute about 80% of all dosage forms.  They are used to produce systemic action.  A tablet is a unit dosage form of medication containing one or more drugs to which excipien...

LECTURE 2 TABLET (1)  2  Tablets  Solid dosage form comprises tablets and capsules constitute about 80% of all dosage forms.  They are used to produce systemic action.  A tablet is a unit dosage form of medication containing one or more drugs to which excipients are added and compressed as granules or powder to a definite shape.  Advantages of tablets as dosage form: 3  1- Are convenient to use and elegant dosage form. 2- Availability in a wide range of types which offer a range of drug release rates and duration of clinical effect. 3- Tablets may be formulated to release the drug at particular site within G.I.T. promoting the absorption at this site. This could not be done by other dosage forms.  4 4- Formulation of tablets could contain more than one drug even if there is incompatibility between each drug. 5- All classes of therapeutic agent may be administered orally. 6- Ease of masking bad taste by coating. 7- Tablets generally are non expensive. 8- Tablets are more stable chemically, physically or microbiologically than other dosage forms.  Disadvantages of tablets as dosage forms: 5 1- The manufacture of tablets requires many steps of operation and in each step an increased product loss in manufacturing. 2- The drug absorption from tablets depends on physiological factors e.g. gastric emptying rate and show patient variation. 3- The compression of some drugs is poor and may present problems in the manufacture.  6 4- The problem to administer tablets to children and elderly peoples due to difficulty in swallowing.  This problem is solved by using effervescent and chewable tablet.  Types of tablets 7 1- Conventional compressed tablets (C.T.)  These tablets are designed to provide rapid disintegration and hence rapid drug release and represent a significant proportion of tablets clinically used.  These tablets ore manufactured by compressing granules or powders that containing the drug.  On administration by the patient this tablet will disintegrate within G.I.T. allowing the drug to dissolve in the gastric fluid and absorbed.  Types of tablets 8 2- Multiple compressed tablets (M.C.T.)  These are tablets composed of at least two layers and there are two designs; a- Multiple layered  In multiple layered tablets the first layer is formed by light compression of granules containing the drug then a next layer of granules containing the drug is compressed on the first layer.  Types of tablets  b. – Compression coated  The first layer is prepared by light compression then removed and located in a second press machine to feed granules with drug around the formed layer (on the surface & edges) then compressed to form a coated layered tablet.  The inner tablet being the core and the outer portion being the shell. 9  core coat 7 Fig. 7-24. Diagram of multiple- compressed tablets. A, having a core of one drug and a shell of another, and B, a multiple- layered tablet of 10 two drugs.  Types of tablets 11  Application of using the multiple compressed tablets: 1- Separation of incompatible drug in separate layered tablet. 2- The delivery of therapeutic agents at different rates or to different sites within G.I.T. from single tablet. 3- Production of coated tablets with an external layer that irritant to the stomach or unstable in acidic PH.  Types of tablets 12  3- Enteric coated tablets (E.C.T.)  They are tablets coated with a polymer that does not dissolve in acidic conditions (stomach) but dissolve in alkaline conditions of small intestine (pH 7.4)  The polymers used for enteric coating inhibit the dissolution of the drug in the stomach or protect the drug from degradation or protect the stomach mucosa from the irritation caused by some drugs (anti-rheumatics)  Types of tablets 13  Polymers used for enteric coating: 1. Cellulose acetate phthalate (CAP) or cellulose acetate butyrate, the dissolution of the polymer occurs in solution above pH 6. 2. Hydroxyl propyl methyl cellulose succinate (HPMCS): this polymer dissolves in the intestinal secretions. 3. Methacrylic acid co- polymers (Eudragits): it is characterized by presence of a wide range of functional groups which exhibit a range of solubility's.  Types of tablets 14  The available Eudragits which resist dissolution in the stomach such as Eudragits L100 which soluble in intestinal fluids from pH 5.5 and Eudragits S100 which is soluble in the intestinal fluids from pH 7.  4- Sugar coated tablets (S.C.T.)  They are conventional tablets coated with a concentrated sugar solution to improve the tablet appearance or to mask bitter taste of the drug.  Now sugar coated tablets decreased in use for improved techniques of film coated tablets.  Types of tablets 15  5- Film coated tablets (F.C.T.)  These are conventional tablets coated with a polymer or a mixture of polymers.  Film coated with polymers that dissolve in stomach (non enteric) to enable tablet disintegration and dissolution such as: 1- Hydroxyl propyl methyl cellulose (HPMC). 2- Hydroxyl propyl cellulose (HPC). 3- Eudragit E100.  Types of tablets 16  If the film coating is employed to control the rate and duration of drug release in certain region of G.I.T, the drug release occurs by diffusion through the insoluble coating and subsequent partitioning into G.I.T fluids.  Examples of polymers used for this purpose: 1- Ethyl cellulose (EC)  It is insoluble in aqueous solutions at all pH values.  2- Eudragit RS and RL:  Are methacrylate co- polymers that are insoluble in water. The RS differs from RL in the ratio of monomers.  Types of tablets 17  6- Chewable tablets These are tablets that chewed within the buccal cavity prior to swallowing and applied mainly for:  Administration to children and adults who have difficulty in swallowing conventional tablets.  Antacid formulations in which the size of the tablet is related to particle size within the stomach.  If the drug taste is not acceptable, it is not recommended to be manufactured in chewable tablet.  pharmaceutical1 Types of tablets 18 7- Effervescent tablets  They are tablets when added to aqueous solutions they will rapid disintegrate with effervescence producing solution or suspension of the drug in aqueous medium.  The disintegration of the tablet is due to a chemical reaction occurs between two component in the presence of water, with the evolution of CO2 which causes the disintegration.  This type of tablets has the advantage of producing a solution ready for absorption in G.I.T.  The main disadvantage is the need of a moisture impermeable package such as aluminum foil to inhibit the interaction between the acid and sodium bicarbonate.  Types of tablets 19 8- Buccal and sublingual tablets:  Are dosage forms that held within oral cavity and slowly dissolve.  The drug is absorbed across the buccal mucosa to produce systemic effect.  Buccal tablets are placed between the cheek and the gingival while the sublingual tablets are placed under the tongue.  These tablets are employed to achieve either rapid absorption & avoiding first pass metabolism.  Buccal and sublingual tablets should be formulated to dissolve slowly in vivo and not disintegrate with retaining in the site of application.  It should not contain components that stimulate the production of saliva.  Types of tablets 20 9- Vaginal tablets  These are ovoid shaped tablets that are inserted into the vagina using a special inserter.  Following insertion retention and slow dissolution of the tablet occur release the therapeutic agent to provide local therapeutic effect, e.g. for the treatment of bacterial or fungal infection. Vaginal tablets may also be used to provide systemic absorption of the drug.  It is important that dissolution & not disintegration of the tablet occurs in vivo.  Manufacture of tablets 21  In this important section we will explain the following: 1- Excipients used in the manufacture of tablets 2- Methods used for the manufacture of tablets 1- Excipients used in the manufacture of tablets:  The following excipients are used in the manufacturing of the conventional tablets: 1- Diluents = fillers = bulking agents 2- Binders 3- Disintegrants 4- Lubricants 5- Glidants 6- Miscellaneous  1- Diluents = fillers = bulking agents 22  They are employed in tablet formulation by any method to increase the mass of the tablets that containing a low concentration of the drug rendering the process of manufacture more reliable and reproducible.  Diluents must exhibit good compression proprieties and not expensive such as: 1. Anhydrous fructose 2. Lactose monohydrate 3. Spray dried lactose 4. Starch 5. Dibasic calcium phosphate 6. Microcrystalline cellulose (Avicel®) 7. Mannitol  23 Anhydrous lactose:  Is available in a range of particle sizes & used mainly as diluents in wet granulation & dry granulation. It is a crystalline material. Lactose monohydrate:  It is available in a wide range of grades with different physical properties e.g.: particle size & bulk density. Spray dried lactose: It is a mixture of crystalline α-lactose monohydrate (80- 90 %) & 10-20% amorphous lactose. It is prepared by spray drying a suspension of α-lactose monohydrate. The specific use of spray dried lactose for the manufacture of tablets by direct compression method.  24 Starch:  It is a polysaccharide composed of amylose & amylopectin used as diluent, binder & disintegrants.  Pregelatinized grade is available in which the granules of starch physically & chemically modified to produce free flowing powder (granular starch) Dibasic calcium phosphate:  It is available as different hydrate forms with range of particle sizes. It is a basic excipient & may react with acidic component in presence of moisture. It has an excellent flow & compression properties.  25 Microcrystalline cellulose ( MCC):  It is crystalline powder prepared by controlled hydrolysis of cellulose. Different grades are present that differ in physical & chemical properties such as density, flow properties & particle size distribution. E.g.: Avicel PH- 101 (powder) & Avicel PH- 102 (granular). Mannitol:  It is a polyol used as diluents specially for chewable tablets due to its sweetness. It has excellent flowability.  2. Binders (Adhesive) 26 Role:  To bind powders together in the wet granulation process  To bind granules together during compression Example of commonly used binders: 1. Solution binders as starch, sucrose and gelatin. 2. Dry binders as microcrystalline cellulose and cross linked pvp.  Types of binders sugars Polymeric materials Natural polymers Synthetic polymers Starches, gums and Methyl, ethyl, hydroxypropyl gelatin cellulose and pvp. 27  Different Ways to add a Binder: 28 1. Solution binder  As a dry powder which is mixed with the other ingredients before wet granulation. Mechanism of action: During the granulation procedure the binder dissolves partly or completely in the liquid; as a solution which is used during wet agglomeration. 2. Dry binder As a dry powder which is mixed with other ingredients before compaction. Both binders are included in the formulation at low concentrations, 2 – 10 %.  3- Disintegrants 29  They are employed to facilitate the breakdown of the tablet granules upon entry into the stomach.  The disintegrant is essential in hydrophobic tablets with high compression force to enable disintegration within the pharmacopeia standards (15 minutes for conventional tablets)  Mechanisms of disintegration: 30 Disintegrant would swell in gastric fluids and exert sufficient mechanical pressure within the tablet to cause it to break apart into small segments and thus hasten the absorption by increasing surface area of particles. These disintegrants are mainly hydrophilic polymers. Ex. sodium starch glycolate, croscarmelose sodium (a cross-linked sodium carboxy methyl cellulose) (0.5 - 5%),  4- Lubricants 31  Lubricants act at the interface between the face of the die and the surface of the tablets to reduce the friction at the interface during ejection of the tablet from the tablet press.  Insufficient lubricant will lead to tablet defects, where high conc. of lubricant will lead to reduced disintegration and dissolution.  In addition, the time of mixing of lubricant with granules as well as the particle size of the lubricant will affect the performance of the lubricant. Over mixing may adversely affect tablet disintegration & drug dissolution.  Mixing of disintegrant & insoluble lubricant together should be avoided for this should form a film of lubricant on the disintegrant surface which reduce wettability of disintegrant  32  There are 2 main categories of lubricants: 1- Insoluble lubricants:  They are added to the final mixing stage before tablet compression.  The efficacy of lubricant is enhanced if its area is increased (decrease the particle size).  Examples of insoluble lubricant material: 1. Magnesium stearate (0.25 - 0.5 % w/w) 2. Stearic acid (1 – 3 % w/w)  33 2- Soluble lubricants:  They are used to overcome the bad effects of insoluble lubricant on the tablet disintegration & drug dissolution, although the effect of insoluble lubricant is superior than the soluble lubricants. Examples:  1. PEG 4000, 6000 or 8000 grades.  2. Sodium lauryl sulfate 1- 2 % w/w.  5- Glidants 34  They act to enhance the flow properties of powders within the hopper & into tablet die in the tablet press.  To achieve this effect the Glidants must be small in particle size and to be arranged on the surface of the granules.  Their concentration must not exceed the recommended as it is hydrophobic & may affect the disintegration of the tablet and the dissolution of the drug.  Examples:  1. Talc (0.5- 3 % w/w)  2. Colloidal silicon dioxide (0.1 - 0.5 % w/w)  6- Miscellaneous excipients 35 (1) Adsorbents  They are included to be adsorbed a liquid or semisolid component when incorporated within the tablet formulation. Ex. Magnesium oxide or carbonate and kaolin or bentonite. (2) Sweetening agent / flavors  They are incorporated to control the taste and tablet acceptability especially chewable tablets if the components have disagreeable taste.  36 (3) Colors  They are used to improve the tablet appearance or to identify the finished product.  The color must be distributed well throughout the tablet by adding a water soluble color to the granulation liquid in wet granulation method. (4) Surface active agents  They are added to improve the wetting properties of hydrophobic tablets increasing the rate of tablet disintegration.  Also they are added to increase the solubility of poorly soluble drug in G.I.T hence increasing the rate of tablet dissolution e.g: Sodium lauryl sulfate. Thank you