Multiple Unit Tablets

Today, the tablet is a dominant dosage form, since it is convenient to administer and relatively easy to mass- produce. More ever, it is the dosage form of first hand choice in the development of new drug entities. Tablets are usually prepared by applying to powder bed, there by compressing it in to a coherent compact. 
          
Controlled release formulations in tablet form are many but over the years the Microsphere formulations have immense popularity owing to their superiority over the former in several respects.

•    Controlled absorption with resultant reduction in peak to trough ratios.
•    Targeted release of the drug to specific areas within the Gastro intestinal tract.
•    Absorption of drug irrespective of the feeding state.
•    Minimal potential for dose dumping.
•    Facility to produce combination dosage form, etc

As a solid Multiple –unit dosage form, microsphere and microcapsules may be filled in to a hard gelatin capsules or be compressed in to a tablets. It is recognized that a multiple–unit controlled release tablet dosage form presents a better alternative to a single unit system for oral formulation.

An ideal multiple-unit tablet dosage form is the one, which in oral administration, disperse or disintegrate rapidly in stomach to release a large number of drug particles, granules, and spheroids. That has maintained the integrity of both cores, and their release- retarding properties such that their drug release kinetics is unaltered.

Peroral controlled-release multiple unit dosage forms (e.g., pellets, granules or microspheres, microcapsules, microparticles) are becoming more and more important on the pharmaceutical market, as they provide several advantages compared to single-unit dosage forms (e.g., tablets or capsules) . A multi-unit controlled release tablet dosage form offers several advantages in comparison to capsules.

•    Small size of the unit enabling the preparation to be swallowed easily
        (i.e. ease of esophageal transit as compared to large size capsules)
•    Ability to administer a portion (dose division) of such multiple-unit tablets   with out compromising their controlled release properties
•    Ability to incorporate large dose of drug in controlled release form in comparison to capsules.
•    Lesser cost of formulation and production as compared to capsules.
•    Feasibility of using existing tabletting capacities in the manufacturing set up.
•    Greater stability of drug and the formulation owing to small size and absence of gelatin shell.
•    Ability to formulate such tablets in a dispersible base that can be reconstituted during use to form a   suspension that can be easily   swallowed and hence suitable for children and elderly.
•    Lesser tendency for product tampering.
•    Controlled- delivery or large doses of biologically active ingredient is also possible in this way and is thus advantageous in comparison to tablets and capsules,  which owing to their size will be   difficult  to swallow and in comparison to chewable tablets, where chewing would result in loss of controlled release characteristics.

Compaction of beads, pellets or spheroids in to tablets has always been of interest the type and amount of coating the size of subunit, the surface properties of pellets, the selection of external and internal additive having a cushioning effect and the rate and magnitude or applied pressure must be carefully considered in the design of such a dosage form. 
 
 A multiple-unit dosage form has more homogenous individual plasma profiles, shorter lag time and lower variability as compared to single unit   formulations. Generally sustained release and gastric resistant preparations can be administered in a single unit dosage form, whereas Multi-component drug delivery system is available in capsules form. Multiple-unit systems also have numerous therapeutic advantages over single unit dosage form when taken orally. Multiple-unit system generally disperse freely in the gastrointestinal fluids, maximizes absorption, minimizes side effects and reduce inter and intra patient variability.

Oral controlled release multiple unit dosage forms such as beads, pellets and microparticles are becoming more popular than single unit dosage forms. These systems tend to spread uniformly throughout the gastrointestinal tract (GIT) 7. High local drug concentration and the risk of toxicity due to locally restrained tablet can be avoided.

Multiple unit dosage forms avoid the vagaries of gastric emptying and different transit rates and, thereby, release the drugs more uniformly. The uniform distribution of these multiple unit dosage forms along the GIT could result in more reproducible drug absorption and reduced risk of local irritations than the use of single unit dosage forms.

The Multiparticulate can be filled into hard gelatin capsules or compressed into tablets. The compression of multiparticulate into tablets is becoming more popular, especially in the US, where the hard gelatin capsules have been tampered with Tylenol 9. Risks such as spontaneous drug release from a single-unit tablet due to damaged coating or its attachment in the stomach or intestine causing an irritation of the gastric or intestinal mucosa are reduced by the use of multiunit forms 10.

After disintegration of the tablets in the stomach, single units equal to or below 2 mm in diameter and having a density lower than 2.5 g/cm3   behave like a liquid and have a short transit time through the stomach avoiding drug accumulation11.

Moreover, such small single units enable a more reproducible dispersion throughout the gastrointestinal tract leading to a reduction of drug release variations and an improved bioavailability. Thus, it results in a decrease in drug dose and side effects 12, 13 .With regard to the final dosage form, the multiparticulate can be filled into hard gelatin capsules14 or be compressed into disintegrating tablets 15, 16, 17, the advantages of tabletting multiparticulates include less difficulty in esophageal transport, and thus a better patient compliance. Tablets can be prepared at a lower cost because of the higher production rate of tablets presses.

The expensive control of capsule integrity after filling is also eliminated. In addition, tablets containing multiparticulates could be scored without losing the controlled release properties, which allows a more flexible dosing regimen18,19,20.