TABLET DILUENTS(LACTOSE AND CALCIUM PHOSPHATE)

MD.JAKIUL ISLAMID:UG08-20-12-066

CONTENTS

Definition

Properties of diluents

Purpose of diluents

classification

What is diluent ?????

Diluents are fillers used to increase the bulk volume of a tablet

diluent

active pharmaceutical ingredients

product adequate weight and size

Purpose of diluents :• to enhance bulkiness

• to provide improved cohesion

• to enhance flow

• to allow direct compression manufacturing

Properties of diluents:

• inert

• nontoxic

• biocompatible

• stable

• acceptable

• non-hygroscopic

• non-conducive to microbiological

• commercially available in acceptable grades

• color-compatible

• no deleterious effect on bioavailability of drugs.

Classification :Diluents

Chemical nature Solubility

Organic materials Inorganic materials Insoluble Soluble

DextroseLactoseMannitolSorbitolStarchsucrose

Calcium phosphate (II)Calcium phosphate (III)Calcium sulphateCalcium carbonate

DextroseLactoseMannitolSorbitolsucrose

Calcium phosphate (II)Calcium phosphate (III)Calcium sulphateCalcium carbonateStarch

Compatibility

Flowability

Solubility

disintegration qualities

hygroscopicity

lubricity

stability

SELECTION OF DILUENT

EFFECTS OF DILUENTS:

• Degradation of API (hydrolysis)

• Mannitol - punch filming/ picking

• Sucrose – tablet hardness-poor disintegration

• Capping – low moisture

• complex formation

LACTOSE :

• solubility – water soluble

Forms

Hydrous

Anhydrous

used in wet granulation

shows fast disintegration, good friability, practically no sticking, binding and capping

• most widely used diluent

hydrous form undergoes maillard reaction discoloration of certain drugs

( amine drug )

● Problem of browning due to contamination of 5-hydroxyfurfural which was accelerated in the presence of basic amine drugs and catalyzed by tartarate, citrate and acetate ions

Inorganic calcium salts

• Dicalcium phosphate (Emcompress or DiTab)

Free flowing aggregates of small microcrystals that shatter upon compaction

Inexpensive and possesses a high degree of physical and chemical stability

Non hygroscopic at a RH of up to 80%

Good fluidity

Slightly alkaline with a pH of 7.0 to 7.3

• Tricalcium phosphate (TriTab) is less compressible and less soluble, higher ratio of calcium ions

MAK95

Tribasic Calcium Phosphate

As with dibasic calcium phosphate, a lubricant and a disintegrant should usually be incorporated in capsule or tablet formulations that include tribasic calcium phosphate. In some cases tribasic calcium phosphate has been used as a disintegrant. It is most widely used in vitamin and mineral preparations as a filler and as a binder. It is a source of both calcium and phosphorus, the two main osteogenic minerals for bone health.

Trade name:• Dibasic calcium phosphate : Di-Tab and Emcompress

• Anhydrous dibasic calcium phosphate : A-Tab, Fujicalin, Emcompress Anhydrous

• Tribasic calcium phosphate : Tri-Tab.

Lactose monohydrate, spray dried lactose and anhydrate lactose are widely used as diluents:

Spray dried lactose :● Lactose is placed in aqueous solution, removed impurities and spray dried

● Mixture of large alpha monohydrate crystals and spherical aggregates of smaller crystals

● Good flow ability but less compressibility

● Poor dilution potential

● Trade name: Spray Process 315; Flow Lac; Lacto press; Super Tab 11SD,14SD etc.

Fast-Flo lactose (early 1970s)

●Spherical aggregates of microcrystals lactose monohydrate

●Much more compressible

●Non hygroscopic

●Tablets are three to four times harder than regular spray dried

SuperTab® 11SD SuperTab® 11SD is a DFE Pharma key range product.

Lactose monohydrate - SuperTab® 11SD (EU)• Complies with the latest editions of USP-NF, Ph. Eur & JP.• Production location: DMV-Fonterra Excipients GmbH & Co.KG, Nörten

Hardenberg, Germany.• Standard packaging size: 40 kg HDPE drum with PE inner liner.• Shelf life: 2 years. Lactose monohydrate - SuperTab® 11SD (NZ)• Complies with the latest editions of USP-NF, Ph. Eur &JP.• Production location: Fonterra Limited, Kapuni, New Zealand.• Standard packaging size: 30 kg carton box with PE inner liner.• Shelf life: 2 years.

What is Lactose Monohydrate?

Lactose (C12H22O11) is milk sugar. It is a disaccharide

composed of one galactose and one glucose molecule. In the

pharmaceutical industry, lactose is used to help form tablets

because it has excellent compressibility properties. It is also

used to form a diluents powder for dry-powder inhalations.

Lactose may be listed as lactose hydrous, lactose anhydrous,

lactose monohydrate, or lactose spray-dried.

Characteristics of a –Lactose monohydrate (hydrous)

• Lactose monohydrate is not directly compressible and therefore it is suitable for use in wet granulation.

• It has poor flow properties and water soluble

• Lactose is odorless and slightly sweet-tasting; a-lactose is approximately 20% as sweet as sucrose

• It produces a hard tablet and the tablet hardness increases on storage, disintegrant is needed in formulation.

• Drug release rate is usually not affected.

• Occurs discoloration with amines and alkaline materials.

• It contains approximately 5% moisture and hence is a potential source of instability especially with moisture sensitive drugs.

• Trade name: Pharmatose and Respitose®

Pharmatose® 90M  

Lactose monohydrate:• Complies with the latest editions of USP-NF, Ph. Eur & JP.• Production location: Friesland Campina DMV BV, Veghel, The

Netherlands.• Standard packaging size: 25 kg paper bag with PE inner liner.• Shelf life: 3 years.

Anhydrous LactoseA solution of lactose is rapidly dried at high temperature to form anhydrous lactose which is then milled and sieved to the required particle size distribution. Anhydrous lactose offers the best compact ability of all grades of lactose, and it is well suited to direct compression applications. Anhydrous lactose is also well suited for formulations containing moisture sensitive drugs, due to the absence of crystal water. It is the recommended form of lactose for dry granulation because its brittle nature allows re-compaction without loss of tablet ability. DFE Pharma offers anhydrous lactose under the brand names Lacto press® Anhydrous and Super Tab® AN. The specialty range products offer a selection of particle size distributions for improved flow or low dusting.

Characteristics of Lactose anhydrous

• Lactose anhydrous is a directly compressible diluents.

• It does not exhibit free flowing property.

• It can pick up moisture at elevated humidity as a result of which changes in tablet dimensions may occur.

• Anhydrous lactose can be used with moisture-sensitive drugs due to its low moisture content.

• Anhydrous lactose typically contains 70–80% anhydrous b-lactose and 20–30% anhydrous a-lactose.

• It is inexpensive.

• Trade name : Pharmatose® DCL 21, Super Tab 21AN

Super Tab® 21AN

Super Tab® 21AN is a DFE Pharma key range product.

1.Complies with the latest editions of USP-NF, Ph. Eur. & JP.2.Production location: DMV-Fonterra Excipients GmbH & Co.KG, Nörten Hardenberg, Germany.3.Standard packaging size: 50 kg HDPE drum with PE inner liner.4.Shelf life: 2 years.

Anhydrous lactose