Journal of Pharmaceutical and Biological Sciences

Journal of Pharmaceutical and Biological Sciences ISSN: 2320-1924; CODEN: JPBSEV Published by Atom and Cell Publishers © All Rights Reserved Available online at: http://www.jpabs.org/ Review Article

Immediate release drug delivery system-A novel drug delivery system 1

Debjit Bhowmik*, 1Amrendra Singh, 1Darsh Gautam 2K.P. Samapth Kumar

1

Himachal Institute of Pharmacy Education and Research, Naudan, Bela, Hamirpur, Himachal Pradesh, Pin-177033, India. 2 Department of Pharmacy, Coimbatore Medical College, Coimbatore, Tamil Nadu, India Received: 21-08-2016 / Revised Accepted: 07-10-2016 / Published: 29-10-2016

ABSTRACT An Oral Dosage Form is the physical form of a dose of a chemical compound used as a drug or medication intended for administration or consumption by oral route. Common oral dosage forms are tablets or capsules. Tablets are solid preparations each containing a single dose of one or more active substances with or without excipients usually obtained by compressing uniform volumes of particles. Tablets are intended for oral administration. Some are swallowed whole, some after being chewed, some are dissolved or dispersed in water before being administered and some are retained in the mouth where the active substance is liberated. The excipients can include binders, glidants and lubricants to ensure efficient tabletting; disintegrants to promote tablet break-up in the digestive tract; sweeteners or flavors to enhance taste; and pigments to make the tablets visually attractive. These are included in the formulations to facilitate easy handling, enhance the physical appearance, and improve stability and aid in the delivery of the drug to the blood stream after administration. A polymer coating is often applied to make the tablet smoother and easier to swallow, to control the releaserate of the active ingredient, to make it more resistant to the environment (extending its shelf life), or to enhance the tablet's appearance. Keywords: Immediate release dosage form, quick onset of action, stability and bioavailability

INTRODUCTION The need for new oral drug delivery system continues, due to poor patient acceptance for invasive methods, need for exploration of new market for drugs and coupled with high cost of disease management. Developing new drug delivery techniques and utilizing them in product development is critical for pharmaceutical companies to survive this century. An immediate release dosage form allows a manufacturer to extend market exclusivity, while offering patients a convenient dosage form or dosage regimen. Immediate Release Tablets are those tablets which are designed to disintegrate and release their medication with no special rate controlling features, such as special coatings and other techniques. Recently immediate release tablets have started gaining popularity and acceptance as a drug delivery system, mainly because they are easy to administer, has quick

onset of action is economical and lead to better patient compliance. They are also a tool for expanding markets, extending product life cycles and generating opportunities. Advantages of Immediate Release  Economical and cost effective.  Quick onset of action.  Suitable for industrial production.  Improved stability and bioavailability.  Provides some advantages of liquid dosage forms.  Adaptable and amendable to existing processing and packaging machinery.  Unique product differentiation Disadvantages of Immediate Release Tablets  Rapid drug therapy intervention is not possible.  Sometimes may require more frequency of administration.  Dose dumping may occur.

*Corresponding Author Address: Debjit Bhowmik, Himachal Institute of Pharmacy Education and Research, Naudan, Bela, Hamirpur, Himachal Pradesh, Pin-177033, India; E-mail: [email protected]

Debjit et al., J Pharm Biol Sci 2016; 4(6): 197-202

 Reduced potential adjustment.

for

accurate

dose

Procedure:Step 1: Pre milling of formulation components. Step 2: Mixing of the therapeutic agent with the powdered excipients (including thelubricant). Step 3: Compression of the mixed powders into tablets.

METHODS OF FORMULATING IMMEDIATE RELEASE TABLETS In general, the choice of method for the manufacture of tablets is dependent on anumber of factors like:a) The physical and chemical stability of the therapeutic agent during the manufacturing process. b) The availability of the necessary processing equipment. c) The cost of the manufacturing process and d) The excipients used to formulate the product.

Advantages: Direct compression is more suitable for moisture and heat sensitive drugs, since it eliminates wetting and drying steps and increases the stability of active ingredients by reducing detrimental effects.  Changes in dissolution profiles are less likely to occur in tablets made by direct compression on storage than in those made from granulations.  It is suitable for low dose drugs.  Saving equipment, space and personnel.  Fewer formulation excipients.  Better physical and chemical stability.  Superior tablet disintegration.  Shorter “time to market”.  The high compaction pressure involved in the production of tablets by slugging or roller compaction can be avoided.  The chances of wear and tear of punches and dies are less.  Materials are "in process" for a shorter period of time, resulting in less chance for contamination or cross contamination, and making it easier to meet the requirement of current good manufacturing practices .  Due to fewer unit operations, the validation and documentation requirements are reduced.  Due to the absence of water in granulation, chance of microbial growth is minimal in tablets.

1) Direct Compression:The term direct compression is used to define the process by which tablets are compressed directly from powder blends of the active ingredient and suitable excipients which will flow uniformly into a die cavity and form into a firm compact. No pretreatment of the powder blends by wet or dry granulation procedures is necessary. The manufacture of tablets using wet granulation or dry granulation methods is both time-consuming and potentially costly. The mechanisms of particle– particle interactions in tablets produced by direct compression are similar to those operative in tablets produced by dry granulation. The advent of direct compression was made possible by the commercial availability of directly compressible tablet vehicles that possess both fluidity and compressibility. The simplicity of the directcompression process is obvious. But direct compression should not be conceived as a simplified modification of the granulation process for making tablets. It requires a new and critical approach to the selection of raw materials, flow properties of powder blends and effects of formulation variables on compressibility. During the wet granulation process the original properties of the raw materials are, to a great extent, completely modified. As a result, a new raw material is what is finally subjected to compression. Many inadequacies in the raw materials are covered up during the granulation step. This is not true in direct compression and therefore the properties of each and every raw material and the process by which these materials are blended become extremely critical. . Direct compression is often preferred because of its simplicity and relatively low cost, but may not always be technically feasible. It has been estimated that less than 20 percent of pharmaceutical materials can be compressed directly into tablets. The rest of the materials lack flow, cohesion or lubricating properties necessary for the production of tablets by direct compression.

Disadvantages: Direct compression is more prone to segregation due to the difference in density of the API and excipients.  The dry state of the material during mixing may induce static charge and lead to segregation.  Most of the directly compressible materials can accommodate only 30-40 % of the poorly compressible active ingredients like acetaminophen.  API that has poor flow properties and/or low bulk density is difficult to process by direct compression.  There is a need for greater quality control in purchasing of raw material to assure batch uniformity.

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 There is a possibility of material loss during processing due to the transfer of material from one unit operation to another.  There is a greater possibility of crosscontamination than with the directcompression method.  It presents material transfer problems involving the processing of sticky masses.  It can slow the dissolution of drugs from inside granules after tablet disintegration if not properly formulated and processed.

2) Wet granulation:Wet granulation is a process of using a liquid binder to lightly agglomerate the powder mixture. The amount of liquid has to be properly controlled, as over-wettingwill cause the granules to be too hard and under-wetting will cause them to be too soft and friable. Aqueous solutions have the advantage of being safer to deal with than solventbased systems. Procedure:Step 1: The active ingredient and excipients are weighed and mixed. Step 2: A wet granulate is prepared by adding the liquid binder to the powder blend and mixing thoroughly. Step 3: Screening the damp mass through a mesh to form pellets or granules. Step 4: Drying the granulation. Step 5: After the granules are dried, they are passed through a screen of smaller size than the one used earlier. Step 6: After granulation a final lubrication step is used to ensure that the tabletting blend does not stick to the equipment during the tabletting process.

3) Dry Granulation:Dry granulation processes create granules by light compaction of the powder blend under low pressures. The compacts so-formed are broken up gently to produce granules (agglomerates). This process is often used when the product to be granulated is sensitive to moisture and heat. Dry granulation can be conducted on a tablet press using slugging tooling or on a roll press called a roller compactor. Dry granulation equipment offers a wide range of pressures to attain proper densification and granule formation. It is simpler than wet granulation, therefore the cost is reduced. However, this method often produces a higher percentage of fine granules, which can compromise the quality or create yield problems for the tablet. Dry granulation requires drugs or excipients with cohesive properties, and a 'dry binder' may need to be added to the formulation to facilitate the formation of granules. At last powdered lubricants are added.

Advantages: Reduced segregation of formulation components during storage and/or processing, leading to reduced intra- and inter batch variability.  Useful technique for the manufacture of tablets containing low concentrations of therapeutic agent.  Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipient.  Most manufacturing plants are built around wet granulation tablet manufacture.  Tablets produced by wet granulation are amendable to post processing unit operations, e.g. tablet-coating techniques.  A wide variety of powders can be processed together in a single batch and in so doing, their individual physical characteristics are altered to facilitate tabletting.  Bulky and dusty powders can be handled without producing a great deal of dust and airborne contamination.

Advantages: Both roller compaction and slugging require conventional grades of excipients.  These methods are not generally associated with alterations in drug morphology during processing.  No heat or solvents are required. Disadvantages: Specialist equipment is required for granulation by roller compaction.  Segregation of components may occur post mixing.  There may be issues regarding powder flow.  The final tablets produced by dry granulation tend to be softer than  Those produced by wet granulation, rendering them more difficult to process using post-tabletting techniques, e.g. film coating.  Slugging and roller compaction may lead to the generation of dust.

Disadvantages: Because of the large number of processing steps, it requires a large area with temperature and humidity control.  It requires a number of pieces of expensive equipment.  It is time consuming, especially the wetting and drying steps. 199


PROBLEMS IN TABLET MANUFACTURE AND RELATED REMEDIES An industrial pharmacist usually encounters number of problems during manufacturing. Majority of visual defects are due to inadequate fines or inadequate moisture in the granules ready for compression or due to faulty machine setting. Functional defects are due to faulty formulation. Solving many of the manufacturing problems requires an in–depth knowledge of granulation processing and tablet presses, and is acquired only through an exhaustive study and a rich experience.

5) Picking:- ‘Picking’ is the term used when a small amount of material from a tablet is sticking to and being removed off from the tablet-surface by a punch face. The problem is more prevalent on the upper punch faces than on the lower ones. 6) Mottling:- ‘Mottling’ is the term used to describe an unequal distribution of color on a tablet, with light or dark spots standing out in an otherwise uniform surface. 7) Double Impression:- ‘Double Impression’ involves only those punches, which have a monogram or other engraving on them. At the moment of compression, the tablet receives the imprint of the punch. Now, on some machines, the lower punch freely drops and travels uncontrolled for a short distance before riding up the ejection cam to push the tablet out of the die, now during this free travel, the punch rotates and at this point, the punch may make a new impression on the bottom of the tablet, resulting in ‘Double Impression’.

1) Capping and Lamination:- ‘Capping’ is the term used to describe the partial or complete separation of the top or bottom crowns of a tablet from the main body of tablet.‘Lamination’ is the separation of a tablet into two or more distinct horizontal layers. 2) Chipping:- ‘Chipping’ is defined as the breaking of tablet edges, while the tablet leaves the press or during subsequent handling and coating operations. 3) Cracking:- Small, fine cracks observed on the upper and lower central surface of tablets, or very rarely on the sidewall are referred to as ‘Cracking.’

CONCLUSION Immediate release tablets are to give quick onset of action with better patient compliance. In such cases, bioavailability of drug is significantly greater and adverse event is reduced than those observed from conventional tablet dosage form

4) Sticking / Filming:- ‘Sticking’ refers to the tablet material adhering to the die wall. Filming is a slow for of sticking and is largely due to excess moisture in the granulation.

Table 1: Causes and Remedies of Capping and Lamination CAUSES Large amount of fines in the granulation Too dry or very low moisture content (leading to loss of proper binding action) Insufficient or improper lubricant Air entrapment Incorrect adjustment of sweep-off blade

REMEDIES Remove some or all fines through 100 to 200 mesh screen. Moisten the granules suitably. add hygroscopic susbstances e.g: sorbitol,methyl-cellulose or PEG-4000 Increase the amount of lubricant or change the type of lubricant By pre compression Adjust the sweep of blade correctly to facilitate proper ejection.

Table 2: Causes and Remedies of Chipping Causes Remedies Sticking on punch faces Dry the granules properly or increase lubrication Too dry granules. Moisten the granules to plasticize. Add hygroscopic susbstances. Barreled die (centre of the die wider Polish the die to make it cylindrical than ends) Groove of die worn at compression Polish to open end, reverse or replace the die. point

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Table 3: Causes and Remedies of Cracking Causes Remedies Large size of granules. Reduce granules size.Add fines Too dry granules Moisten the granules properly and add proper amount of binder. Tablets expand. Improve granulation add dry binders. Granulation too cold. Compress at room temp [erature. Table 4: Causes and Remedies of Sticking/ Filming CAUSES REMEDIES Granules not dried properly Dry the granules properly,make moisture analysis to determine limits. Too little or improper lubrication Increase or change lubricant. Too much binder Reduce the amount of binder or use a different type of binder. Hygroscopic granular material Modify granulation and compress under controlled humidity. Too soft or weak granules. Optimize the amount of binder and granulation technique. Table 5: Causes and Remedies of Picking CAUSES REMEDIES Excessive moisture in granules Dry properly the granules,determine optimum limit. Too little or improper lubrication Increase lubrication:use colloidal silica as a ‘polishing agent’,so that material doesnot cling to punch faces. Low melting point substances, may Add high melting-point materials. Use soften from the heat of compression and lead to picking. Low melting point medicament in high Refrigerate granules and the entire tablet press. concentration. Too much amount of binder. Reduce the amount of binder, change the type or use dry binders. Embossing or engraving letters on punch Design lettering as large as possible, Plate the punch faces faces such as B, A, O, R, P, Q, G with chromium to produce a smooth and non-adherent face

Table 6: Causes and Remedies of Mottling CAUSES REMEDIES Acoloured drug used along with colorless Use appropriate colorants. or white colored excipients. A dye migrates to the surface of Change the solvent system, change the binder, Reduce granulation while drying. drying temperature and Use a smaller particle size. Improperly mixed dye especially during Mix properly and reduce size if it is of a larger size to direct compression. prevent segregation.

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