Multiparticulate Drug Delivery Systems
Multiparticulates or multiple unit dosage forms are the discrete, small, repetitive units of drug particles which may or may not possess similar drug release pattern. They can be tailored for pulsatile, controlled and or delayed, targeted drug release depending upon the polymer employed in fabrication. A blend of multiparticulates can also be used to provide the desired drug release profile. They are present in the form of microcapsules, beads or pellets or nanoparticles, minitablets out of which pellets have been well investigated. Multiparticulates reduce the risk of dose dumping, systemic toxicity, local irritation and variation in bioavailability as they are less dependent on gastrointestinal transit time. In contrast to monolithic devices, failure of coating will not alter the release behavior as each and every sub unit is coated and damage of single sub unit involved represents a small part of entire dose.
Multiparticulates can be prepared by various methods like pelletisation, granulation, spray drying, spray congealing. Drug can be coated or entrapped into these multiparticulates by powder or solution or suspension layering, compression coating, coacervation, interfacial complexation. Drug is released by diffusion or erosion or osmosis. Multiparticulates can be administered by parenteral or oral route. But, traditionally oral route is the most preferred route of administration by the patients. These multiparticulates can be administered orally in capsule or tablet dosage forms. Most of the multiparticulate systems available in market are present in the form of capsules. If they are compressed in to tablets, the coating may be removed or the release rate may be altered. Elan drug technologies, U.S. intoduced multiparticulate drug delivery systems technologies as SODAS®, IPDAS®, and PRODAS® .
Spheroidal oral drug absorption system (SODAS®):
Various drug release profiles like delayed release, pulsatile release, immediate release followed by sustained release profiles can be achieved depending on the requirements of drug using this technology. Individual beads can be coated with specific controlled release polymers and filled into hard gelatin capsule.
Intestinal protective drug absorption system (IPDAS®):
They were designed to reduce the gastric irritation caused by the irritant drugs like Naproxen. Pellets that are manufactured by different techniques like extrusion-spheronization, solution or suspension layering on to non-pareil seeds can be compressed into a tablet dosage form using this technology. Such a system, when administered into the body by virtue of its multiparticulate nature disintegrates and passes through the gastro intestinal tract in a controlled manner irrespective of the feeding state and hence prevents the irritation. Desired release profiles can be obtained using different polymers and with different concentrations. Naproxen was formulated and marketed using this technology. The product has got another advantage of reduction in dosing frequency from two times daily to once a day and hence minimising the troughs in plasma concentration.
Programmable oral drug absorption system (PRODAS®):
It offers the benefits of both tablets and capsule dosage forms. Mini tablets are filled into hard gelatin capsules. Multiple sites can be targeted within the GI tract and also higher doses of drug can be loaded. Different sizes of mini tablets can be incorporated into the capsule.
Various patented technologies for the production of multiparticulate drug delivery systems are tabulated as follows:
Table: Patented Technologies related to Multiparticulate Drug Delivery Systems S.No. Patented technology Company Drug formulated Brand name Therapeutic Advantage 1
Spherodial oral drug absorption system (SODAS®)
Elan Drug Technologies
Morphine Sulphate Avinza Daily once dose with controlled release for 24hrs with fast onset of action Intestinal protective drug absorption (IPDAS®) Elan Drug Technologies Naproxen
Daily once does with controlled release for 24 hrs, fast onset of action, less irritation in the GI tract Chronotherapeutic oral drug absorption Elan Drug Technologies Veapamil Verelan PM Therapeutic concentrations more during early hours followed by controlled release throughout the day 2 PULSYS Middle Brook Pharmaceuticals Cephalexin Keflex (Phase III on hold) Daily once dose 3 Diffucaps Eurand Cyclobenzapine Amrix Daily once dose Obrexa Eurand Proteins ---- Suitable for high dose of drugs and proteins Eurand minitabs Eurand ----- ---- Tablet multiparticulate system for high dose loading and can also be used to sprinkle on foods for patients that feel difficulty in swallowing 4 Concentric multiparticulate delivery system (CMDS) Imapx Laboratories ---- ---- Control release of multiple active ingredients Timed multiple-action delivery system Impax Laboratories ---- ---- Control release of multiple active ingredients in a programmed manner