You are hereRECENT ADVANCE IN PULSATILE DRUG DELIVERY SYSTEM

RECENT ADVANCE IN PULSATILE DRUG DELIVERY SYSTEM


ADVANCED TECHNOLOGY
Currently pharmaceutical company focused on developing and commercializing pulsatile drug products that fulfil unmet medical needs in the treatment of various diseases. For several diseases (e.g. bronchial asthma, hypertension, rheumatic disease and myocardial infarction) as well for control of body functions (blood pressure, levels of many hormones e.g. aldosterone, rennin, and cortisol) influenced by circadian rhythms, delayed or pulsatile drug release could be an optimal approach.Recently develop various technologies that presents in this review are:

1.      ACCU-BREAK™ TECHNOLOGY
ACCU-BREAK Pharmaceuticals, Inc. ("ABP" or the Company) is a privately-held pharmaceutical company. ABP has invented and is developing the patent-pending ACCU-BREAK family of technologies (the "Technologies"). ACCU-BREAK tablets are designed to improve and enhance the functionality of pharmaceutical tablets. While being manufactured to be easily swallowed as whole tablets, the Company expects ACCU-BREAK tablets to be Simply Better because in addition, they are Made to be Broken. The ACCU-BREAK innovations are designed to allow pharmaceutical tablets to be able to be easily broken into equal half, third, or quarter doses. Accu-Break tablets are manufactured on commercially available multilayer compression equipment. Accu-Break™ Technology is divided in to two types ACCU-B™ Technology and ACCU-T™ Technology.

ACCU-T CR Trilayer Tablets:

Fig.3: ACCU-T CR Tri-Layer Tablets

ACCU-T CR (controlled release) Tri-Layer Tablets configuration applies controlled release technology to further enhance treatment options. The ACCU-T CR tablet contains controlled release medication at either end of the tablet separated by a drug-free break layer, allowing the CR dose to be divided into exact half doses without affecting the rate of drug release. The majority of conventional CR tablets are not suited for subdividing due to the increase of surface area and the subsequent change in release kinetics. ACCU-T technology provides a solution to this problem and introduces dose flexibility into CR dosage forms. Additionally, an IR (immediate release) component can be added to CR tablets to add even more treatment options and potential product capabilities.

ACCU-B Bilayer Tablets:
A second option is the ACCU-B tablet, which comprises a scored top layer pre-divided into four equal segments, plus an inactive bottom layer, which serves asthe breaking region.

2.      AQUALON  SYSTEM
Aqualon CMC EZ products are encapsulated to provide ideal performance in dry mixes and in operations with limited mixing/shear capabilities. Hydrocolloids require dispersion before they can fully hydrate and build viscosity. Dispersion methods like high shear mixing and dry blending add time and complexity to operations. This can be minimized by agglomeration and controlling particle size but at the expense of speed of hydration. Aqualon EZ technology offers both easy dispersion and fast hydration. The drug is contained in the inner (middle) layer of the matrix, with the outer layers providing a predetermined delay in release of the drug. A number of studies have been published where tablet cores were coated with directly compressed ethylcellulose (EC), forming a non-swelling, insoluble diffusion barrier to achieve either sustained release or time-controlled, delayed release profiles. Finely powdered (micronized) EC was particularly effective since the smaller particle size renders the material more compatible.

Features and Benefits:
·         No lumps
·         Easy dispersion significant     mixingor highshear is not needed
·         Fast hydration – full viscosity in a      fraction of the time needed for standard cellulose gum
·         Improved performance in dry mix beverage applications
·         Ideal for operations where shear and mixing capabilities are limited

3.      BANNER’S  VERSETROL™  TECHNOLOGY (Patent No: US650045)
Banner is a global polymer based drug delivery and specialty pharmaceutical company. VersetrolTM Technology is novel innovative technology that provides time controlled release for wide range of drug. In this technology drug is incorporated in lipophillic or hydrophilic matrix and that is than incorporated in soft gelatin capsule shell. This technology is versatile because depending on physiochemical properties of drug either emulsion or suspension can be developed. For lipophillic drugs suspension formulation is preferred while for hydrophilic drugs emulsion form is utilized. By applying combination of lipophillic and hydrophilic matrices desire release profile can be achieved. The utility of the Versetrol™ technology is greatly enhanced because it combines a versatile controlled release technology with the benefits of a customer preferred dosage form.

Versetrol controlled release softgels combine the qualities of a consumer preferred dosage form with the ability to control the release rate of active ingredients. Versetrol offers the flexibility to develop almost any release profile by simply tailoring the formulation variables, resulting in a more predictable release profile. Versetrol™ is a unique oral controlled release technology for the pharmaceutical market place. When combined with softgels, controlled release technology provides a consumer preferred dosage form with the ability to tailor release profiles for a wide variety of drugs. Versetrol™ offers controlled release formulations with the benefits of greater effectiveness in the treatment of chronic conditions by reducing side effects through minimizing peak plasma concentrations, and greater convenience leading to higher levels of patient compliance due to a simplified dosage schedule. Versetrol™ technology can be applied early on in pharmaceutical product development, leading to the parallel development of immediate release and controlled release for mutations to maximize market exposure.

Features:

  • Unique, proprietary technology
  • Novel,innovative controlled  releasetechnology system
  • Depending onthe physicochemical    properties of the compound,   an emulsion or suspension is chosen as the formulation
  • Varying proportions of hydrophilic and hydrophobic components    can be added to the formulation matrix to provide a tailored release profile including a dual release profile
  • Good option for moisture sensitive drugs, due to inherent hydrophobic environment in the fill
  • Ability to engineer to almost any desired release profile
  • Unique matrix formulations for both lipophilic and hydrophilic compounds
  • Compatible with EnteriCare® enteric softgels and absorption enhancement techniques
  • Consumer preferred dosage form

Benefits:

  • Provides first to market opportunity for lifecycle extension and brand building
  • Provides market protection for new products
  • VersetrolTM technology may be applied to difficult to solubilize compounds

4.      CODAS™  TECHNOLOGY (Patent No: US6500459)
In certain cases immediate release of drug is undesirable. A delay of drug action may be required for a variety of reasons. Chronotherapy is an example of when drug release may be programmed to occur after a prolonged interval following administration. Elan’s Chronotherapeutic Oral Drug Absorption System (CODAS™ Technology) was developed to achieve this prolonged interval. Elan’s drug delivery technology can be tailored to release drug after a predetermined delay. The CODAS™ drug delivery system enables a delayed onset of drug release, resulting in a drug release profile that more accurately compliments circadian patterns.

CODAS™ Product Development:
Elan’s Verelan® PM represents a commercialized product using the CODAS™ technology. The Verelan® PM formulation was designed to begin releasing Verapamil approximately four to five hours post ingestion. This delay is introduced by the level of release controlling polymer applied to the drug loaded beads. The release controlling polymer is a combination of water soluble and water insoluble polymers. As water from the gastrointestinal tract contacts the polymer coat beads, the water soluble polymer slowly dissolves, and the drug diffuses through the resulting pores in the coating. The water insoluble polymer continues to act as a barrier, maintaining the controlled release of the drug. When taken at bedtime, this controlled onset extended release delivery system enables a maximum plasma concentration of Verapamil in the morning hours, when blood pressure normally rises from its overnight low.

5.      COLAL TECHNOLOGY (Patent No: WO03068196)
COLAL® involves a coating for drug pellets, tablets or capsules which is composed of ethylcellulose and a form of starch called 'glassy amylose'. The glassy amylose is not digested by human enzymes as the preparation moves down the GI tract, but is digested by bacterial enzymes that are found only in the colon. When the coated product reaches the colon, the coating is degraded, allowing the drug to be released. This technology useful for to Treat Ulcerative Colitis administered Directly to the Colon Completed Phase III Development.In ulcerative colitis, inflammation occurs in areas of the colon and rectum causing pain, diarrhoea and bleeding. Current treatment includes an aggressive therapy for short periods with an antiinflammatory steroid (usually prednisolone) to induce remission of the disease and the use of less potent antiinflammatories over longer periods for the maintenance of the disease in remission. However, the use of anti inflammatory steroids is restricted by their systemic side effects. The worldwide market for ulcerative colitis drugs is estimated to be worth at least $500 million per annum. A product with a substantially improved safety/efficacy profile over existing treatments would be clinically and commercially attractive.

COLAL® comprises a prednisolone derivative (prednisolone sodium metasulphobenzoate) in Alizyme's proprietary colonic drug delivery technology, COLAL®. Data from Alizyme's Phase II trial with COLAL®, indicated that through the local delivery of this drug, the undesirable side effects such as immuno suppression, associated with the use of steroids are avoided.

6.      DIFFUTAB®  TECHNOLOGY (Patent No: US650045)
Multiparticulate drug dosage forms are composed of small beads, each small bead further composed of many layers. Some layers contain drug substance; others are rate controlling polymers. With Eurand’s Diffucap® multiparticulate system, customized drug release profiles are created by first layering active drug onto an inert core (such as a cellulose sphere), then applying one or more rate controlling, functional polymers, to produce spherical, multilayered particles. The drug layering process can be conducted either from aqueous or solvent based drug solutions. Diffutab® technology work on same principle as given below;


Fig.4: Diffutab® technology

Diffutab® technology for sustained release profiles and targeted delivery of pharmaceutical products. This technology incorporates a blend of hydrophilic polymers that control drug release via diffusion through, and erosion of, a matrix tablet. The Diffutab technology is particularly useful for the development of high dosage products and is an effective way to develop sustained release, once a day dosage forms.

Advantages:

  • Matrix tablet utilizes a combination of water soluble particles and active drug
  • Suitable for high drug loading
  • Supports sustained release, once a day dosing

7.      DMDS  TECHNOLOGY
DMDS (Dividable Multiple Action Delivery System) is designed to provide greater dosing flexibility that improve product efficacy and reduces side effects. Traditional controlled release tablet often lose their controlled release mechanism of delivery once it broken. But DMDS technology allows tablet to be broken down in half so that each respective portion of the tablet will achieve exactly the same release profile as the whole tablet. This allows the patient and physician to adjust the dosing regimen according to the clinical needs without compromising efficacy.

8.      EGALET®TECHNOLOGY
Egalet has pioneered one of the world’s first erosion based delivery technologies to enable the controlled release of drugs through gradual erosion of a tablet.  In addition, the Egalet® technology, a novel, patented drug delivery platform, was designed to resist tampering, to prevent easy extraction and to deter the abuse of medications via known routes of abuse, including chewing, snorting, and injecting. The uniquely shaped, patient friendly tablet consists of matrix and can add a shell or coat.  By altering the composition of the shell and matrix, a variety of release formulations can be produced.  The technology offers a predictable and tailored pharmacokinetic profile, lacks a significant food effect and alcohol dose dumping, and can be used with a broad range of opioids and nonopioids.  Egalet has extensively filed patents to protect its inventions covering both the technology and product specific patents. The Egalet® Time Release consists of three compartments: a coat, a drug release matrix and a lag component. The drug is contained in the inner (middle) layer of the matrix, with the outer layers providing a predetermined delay in release of the drug.


Fig.5: Egalet® Two-Part Oral System

1.         Egalet tablet begins
2.         Egalet tablet during release
3.         Egalet tablet has released almost completely

9.      EURAND  MINITABS®  TECHNOLOGY
Eurand Minitabs® is a registered trademark used for Pharmaceutical Carrier Preparation with Sustained Release Properties. Eurand Minitabs® technology combines the simplicity of tablet formulation with the sophisticated drug release control offered by multiparticulate drug forms. Eurand Minitabs are tiny, approximately 2 mm in diameter, cylindrical tablets. Functional membranes may be applied to the tablets to further control release rate. Eurand Minitabs offer high drug loading, a wide range of release rate designs, and fine tuning of these release rates. Capsules containing the Eurand Minitabs can be opened and the contents used as a “sprinkle” formulation. The tablets are filled into capsules, allowing a combination of multiple drugs and/or multiple release profiles in the same dosage form. The Eurand Minitabs® can be formulated as matrix tablets prior to further coating.


Fig.6: Eurand minitabs®  technology

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