Manufacturing of Tablet

Tablets are prepared by compressing uniform volumes of particles or particle aggregates produced by granulation methods. In the manufacture of tablet cores means ensuring that they process a suitable mechanical strength to resist handling without crumbling or breaking. These may be demonstrated by examining the friability of uncoated tablets and the resistance to crushing. Chewable tablets are taken to ensure that they are crushed by chewing.

The manufacture of granule for tablet compression may follow one or a combination of three established methods -

(a) The dry methods of direct compression

(b) Compression granulation

(c) Wet granulation                                                                                                                                                                                     

(a) Direct compression

The vast majority of medicinal agents are rarely so easy to tablet, however in addition the compression of a single substance may produce tablets that do not disintegrate. If disintegration is a problem, the components are needed which in turn may interface with the compressibility of the active ingredient.

(b) Compression granulation (Slug process)

This is a valuable technique in situations where the effective dose of a drug is sensitive to heat moisture or both, which precludes wet granulation. Many aspirin and vitamin for mutations are prepared for tabletting by compressing granulation. Compression granulation involves the compaction of a tablet press or specially designed machinery, followed by milling and screening prior to find compression into a tablet. When the initial blend of powders is forced into the dyes of a large capacity tablet press and is compacted by means of flat faced punches, the compacted masses are called slugs, and the process is referred to as slugging. The slugs are then screened or milled to produce a granular form which now flows more uniformly than the original powder mixture.

 (c) Wet granulation

This technique uses as same as the two previously discussed granulation technique. The unique portion of wet granulation process involves the wet massing of the powder, wet sizing and drying.

Chemical Used for Manufacturing Tablet

Two types of chemical is used for manufacturing a table

     1. Active ingredients

     2. Excipients

1. Active ingredients: the active or necessary chemical for a specific medicine. As an example, for SILPOL (paracetamol) tablet the active ingredient is paracetamol.

2.  Excipients

Regardless of how tablets are manufactured, conventional oral tablets for ingestion usually contains the same classes of components in addition to the active ingredients, which are one or more agents functioning as:

                A • Diluents

                B • Binder or an adhesive

               C • Disintegrate

               D • Lubricant

In some tablet formulations may additionally require a flow promoter other more optional components include colorants and in chewable tablets, flavors and sweetness. All non-drug components of a formula are termed excipients. Some common tablet excipients are given below:

A. Diluents

 Microcrystalline cellulose, often referred to by the trade name Avicel, is a direct compression. Two tablets grades exist p1-1101 (powder) and pH 102 (granules).The flow properties of the materials are generally good and the direct compression characteristics are excellent. This is some what unique diluents in that while producing cohesive compacts, the materials also act as a disintegrating agent. It is however; relatively expensive used as diluents in high concentration and is thus typically combined with other material. As in the case of starch, microcrystalline cellulose is often added to tablet formulation for several possible functions. It is commonly employed exipients.

B. Binders and Adhesives

These materials are added either up or in liquid form during wet granulation to form granules or to promote cohesive compressed tablets.

C. Disintegrates

A disintegrate is added to most tablet formulation to facilitate a breakup or disintegration of the tablet when it contacts water in the gastrointestinal tract.

D. Lubricant, Antiadherent and Glidants

Lubricants are intended to reduced the friction during tablet ejection between the walls of the tablet and the die cavity in which the tablet was formed

Antiadherents have the purpose of reducing sticking or adhesion of any of the tablet granulation or powder to the faces of punches or to the die wall.

Glidants are intended to promote flow of tablet granulation or powder materials by reducing friction between the particles.

E. Colors, Flavors and Sweeteners

Colors are used for disguising of off-color drugs, product identification.

 Flavors are usually limited to chewable tablets and uses only for good flavors.

Sweeteners used for sweetening the tablet. Sugar coating is the example of sweeteners tablet.

Brief Description of Various Tablets

Uncoated Tablets

Uncoated tablets include single-layer tablets resulting from a single comparison of particles and multilayer tablets consisting of concentric or parallel layers obtained by successive comparison of particles of different composition.

Coated Tablets

Coated tablets are covered with one or more layers of mixtures various substances such as natural or synthetic resins, gums, gelatin, inactive and insoluble ifilers, sugars, plasticizers, polyols, waxes, coloring matters, flavoring substances. The substances used as coatings are usually applied as a solution or suspension in conditions in which evaporation of vehicles occurs. When the coating is veiy thin polymeric, the tablets are then known as film coated tablets.

Effervescent Tablets

Effervescent tablets are uncoated tablets generally containing acid substances and carbonates on hydrogen carbonates which reacts rapidly in the presence of water to release of C . They are intended to dissolve or to disperse in water before administration.

Soluble Tablet

Soluble tablets are uncoated or film coated tablets. They are intended to be dissolved in water before administration. The solution produced may be slightly opalescent due to added substances used in the manufacture of the tablets.

Dispersed Tablet

These tablets are uncoated or film coated tablets intended to be dispersed in water before administration giving a homogeneous dispersion.

Gastro resistant Tablet

These are modified release tablets that are intended to resist the gastric fluid and to release their active ingredients in the intestinal fluid. They are prepared by converting tablets with a gastro-resistant coating or from granule or particles already covered with a gastro-resistant coating.

Modified Release Tablet

These are coated or uncoated tablets containing special procedures which separately or together are designed to modify the rate or the place at which the active ingredient are released.

TABLET

Tablet contains one or more active ingredients and obtained by comprising uniform volumes of particles. Some are swallowed whole; some after being administered and some are retained in the mouth where the active ingredient is liberated. It may consists of excipients such as diluents, binders disintegrating agents, glidants , lubricants, coloring matters and agents etc.

Tablet end surfaces may be flat or convex. They may have lines or break marks and may bear a symbol or other markings. It may be coated or non-coated. Several categories of tables for oral use may be distinguished:

--Uncoated tablet

--Coated tablet

--Effervescent tablet

--Soluble tablet

--Dispersible tablet

--Gastro-resistant tablet

--Tablets for use in the mouth

--Modified release tablets

HPLC ASSAY METHOD FOR CEFUROXIME

Chromatographic System :

Column               : 25cm x 4.6mm, packed with particles of silica(5µm)

Flow rate             : 1.2ml / minute , so that the resolution factors between the peaks  corresponding to the Cefuroxime axetil diastereoisomers A & B  in solution(4)and between the peaks corresponding to Cefuroxime axetil diastereoisomer A & the Cefuroxime axetil A³ -isomer in  solution (2) are each not less than 1.5.

Wavelength                   : 278nm

Temperature       :Ambient

Injection volume : 20µL

Mobile Phase       : A mixture of 38 volumes of Methanol & 62 volumes of

                               0.2M Ammonium dihydrogen orthophosphate.

 Solution (1) :- Disperse 10 tablets in 0.2M Ammonium Dihydrogen Orthophosphate

previously adjusted to pH 2.4 with Orthophosphoric acid using 10ml per gm of the stated content of cefuroxime . Immediately add sufficient methanol to produce a solution containing the equivalent to 0.5%w/v of cefuroxime and shake vigorously.

Filter and dilute a quantity of the filtrate with sufficient mobile phase to produce a

solution containing the equivalent to 0.025% w/v of cefuroxime.

Solution (2) :- Heat a quantity of solution(1) at 60⁰ C for 1hour or until sufficient impurities (   ⁰   -isomers) have been generated.

 Solution (3) :- Expose  a quantity of solution(1) to ultraviolet light (254nm) for            24 hours or until sufficient impurities (E-isomers) have been generated.             Solution (4) contains 0.03% w/v of Cefuroxime Axetil CRS in mobile phase.

  All solutions containing Cefuroxime Axetil, if not to be used for immediate

  analysis, should be stored in the dark at a temperature 2º & 8º before analysis.

The retention times relative to Cefuroxime axetil diastereoisomer A are approximately 0.9 for Cefuroxime axetil diastereoisomer B , 1.2 for the Cefuroxime

axetil  A³-isomers and 1.7 & 2.1 for E-isomers .The relative standard deviation for the

response factor of Cefuroxime axetil for replicate injections of solution (1) is not more than 2.0%.

Calculate the content of C₂₀H₂₂N₄O₁₀S as the sum of the areas of the two peaks  corresponding to diastereoisomers A & B of Cefuroxime axetil using the declared

Content of C₂₀H₂₂N₄O₁₀S in Cefuroxime axetil CRS. Each mg of Cefuroxime axetil

Is equivalent to 0.8313mg Cefuroxime.

Assay of Montelukast Sodium (UV-VIS)Spectrophotometric Method

Assay of Montelukast Sodium (UV-VIS)Spectrophotometric Method.

Preparation of standard solution : Take 50mg of Montelukast Sodium in a 100ml volumetric flask, add 50ml of water and sonicate . Add 10ml of 1M Sodium

Hydroxide solution and dilute to 100ml with water. Transfer 1ml of this solution in a 50ml volumetric flask and dilute to 50ml with o.1N NaOH solution.

Preparation of sample solution :  Crush and finely powder 20 tablets. Weigh an amount of tablet powder containing 50mg of Montelukast Sodium in a 100ml volumetric flask, add 50ml of water and sonicate for about 10 minutes. Add 10ml of 1M NaOH soln. and dilute to 100ml with water, filter. Transfer 1ml of this solution in a 50ml volumetric flask and dilute to 50ml with 0.1N NaOH soln.

Measure the absorbance of the resulting solution at he maximum wavelength 345nm, using 0.1N NaOH as blank.

                                            Abs. of sample X Wt. of standard

% 0f Montelukast Sodium=---------------------------------------X potency of Standard

                                             Abs.of Std. X    Wt. of sample

HPLC ASSAY METHOD OF ASPIRIN

Preparation of Mobile phase :- Dissolve 2gms of sodium 1-heptasulphonate in a mixture of 850ml of water and 150ml of acetonitrile,and adjust with glacial acetic

acid to a pH of 3.4.

Diluting solution : Prepare a mixture of acetonitrile and formic acid (99:1)

Standard preparation : Dissolve an accurately weighed quantity of USP Aspirin RS in diluting solution to obtain a solution having a known concentration of about 0.5mg/ml

Assay preparation:  Weigh and finely powder not less than 20 tablets. Transfer an accurately weighed quantity of powder ,equivalent to about 100mg of aspirin ,to a suitable container. Add 20ml of diluting solution and about 10 beads. Shake vigorously for about 10 minutes, and centrifuse (Stock Solution).

Quantitatively dilute an accurately measured volume of the stock solution with

9 volumes of diluting solution (Assay preparation).

Chromatographic System :

Column                : 4.0mm X 30cm containing packing L1

Flow rate              : 2ml per minute.

Wavelength          : 280nm.     

Temperature                  : Ambient

Injection volume   : about 10µL.

Procedure : Seperately inject an equal volumes (about 10µL) of Standard preparation and Assay preparation into the chromatograph , record the chromatograms,and measure responses for the major peaks.

Calculate the quantity,in mg,of the aspirin (C₉H₈O₄) in the portion of the

tablets taken by the formula :

                                     200C(ru / rs),

In which C is the concentration, in mg per ml, of USP Aspirin RS in the standard preparation , an ru and rs are the peak responses of the aspirin peaks obtained from

the Assay preparation and the Standard preparation respectively.