CONTIN technology:
In this technology, molecular coordination complexes are formed between a cellulose polymer and a non-polar solid aliphatic alcohol optionally substituted with an aliphatic group by solvating the polymer and reacting the cellulose polymer directly with an aliphatic alcohol. This technology has concretely enabled the tablet forms of sustained release aminophylline, theophylline, morphine.
This technology provides for closer control over the amount drug released to the bloodstream and benefits patients in terms of reducing the number of doses they need to take every day, providing more effective control of their disease and reducing unwanted side effects. (PRITI P. PEDNEKAR 2011)
OROS Technology:
Chronoset™ is proprietary OROS®
(Osmotic‐controlled Release Oral delivery System) developed by Alza Corporation (now part of Johnson and Johnson). The system is composed of two compartments—the drug vessel and the osmotic engine cap. When the system is exposed to
an aqueous medium, water permeates into the osmotic engine cap via a ratecontrolling membrane.
Hydration of the osmotic engine leads to its expansion, which exerts a driving force against the ridge of the drug vessel. The two compartments separate from each other by sliding apart. After disengaging, the open mouth of the drug vessel is exposed to the fluid environment. The Chronoset®
can deliver essentially the entire dose and minimizes the drug residue in the drug vessel after the operation. The vessel is made of waterimpermeable ethylene‐co‐vinyl acetate copolymer (EVA), while the cap is made of proprietary water‐permeable blends of polycaprolactone (TONE) and flux enhancers.
(Maroni A 2005)
Fig.15: OROS Technology (PRITI P.
PEDNEKAR 2011) CEFORM® technology:
Ceform® allows the production of uniformly sized and shaped microspheres of pharmaceutical compounds. These microspheres are almost perfectly spherical, having a diameter that is typically 150 to 180 mm, and allow for high drug content. The microspheres can be used in a wide variety of dosage forms, including tablets, capsules, suspensions, effervescent tablets, and sachets. The microspheres can be coated for controlled release (Ceform CR), provided with an enteric coating (Ceform EC), or combined into a fast/slow release combination (Ceform EA/CR) (PRITI P.
PEDNEKAR 2011).
DIFFUCAPS® technology:
Diffucaps is a multiparticulate bead system comprised of multiple layers of drug, excipients, and release‐controlling polymers. The beads contain a layer of organic acid or alkaline buffer to control the solubility of a drug by creating an optimal pH microenvironment for drugs that exhibit poor solubility in intestinal pH, in
98 environments with pH greater than 8.0, or in physiological fluids. Alternatively, the beads can contain a solid‐solution of drug and crystallization inhibitor to enhance bioavailability by maintaining the drug in its amorphous state. Each Diffucaps bead has an inert core surrounded by drug and coated with a functional polymer membrane to control the rate of drug release. Diffucaps beads are
<1.5 mm in diameter and can be filled into capsules or compressed into orally disintegrating tablets.
(PRITI P. PEDNEKAR 2011) Advantages of Diffucaps:
• Ideal for drugs exhibiting poor solubility in lower intestinal pH, in environments with pH above 8.0, or in physiological fluids
• Can combine multiple drugs and/or multiple release profiles in the same dosage form
• Simple formulation of dose‐proportional strengths.
• Can minimize food effect. (PRITI P.
PEDNEKAR 2011)
Fig.16: Cross section of Diffucaps (PRITI P.
PEDNEKAR 2011)
Fig.17: Diffucap
CHRONOTOPIC® technology:
It consists of a core containing drug reservoir coated by a hydrophilic polymer hydroxylpropylmethylcellulose (HPMC). An additional enteric‐coated film is given outside this
layer to overcome intra‐subject variability in gastric emptying rates. The lag time and the onset of action are controlled by the thickness and the viscosity grade of HPMC. (PRITI P. PEDNEKAR 2011)
Fig.18: Chronotopic Technology (PRITI P.
PEDNEKAR 2011)
EGALET® technology (Egalet Ltd, Denmark):
It offers a delayed release. System consists of an impermeable shell with two lag plugs, active drug is sandwiched between the plugs. After the inert plugs have eroded, the drug is released, thus a lagtime occurs. Time of release can be modulated by the length and composition of the plugs. The shells are made of slowly biodegradable polymers (such as ethylcellulose) and include plasticizers (such as cetostearyl alcohol), while the matrix of the plugs is made up of a mixture of pharmaceutical excipients including polymers like polyethylene oxide (PEO). (PRITI P. PEDNEKAR 2011)
Fig.19: Egalet: (a) Intact Unit (b) Erosion of the time delay insert plugs, and (c) Drug release (PRITI P. PEDNEKAR 2011)
99 CODAS® technology (Elan Drug Technologies, USA):
CODAS(Chronotherapeutic Oral Drug Absorption System) are a multiparticle system designed for bedtime drug dosing, incorporating a 4–5‐hour delay in drug delivery. This delay is introduced by the level of nonenteric release‐controlling polymer applied to drug‐loaded beads. The rate of release is essentially independent of pH, posture, and food.
GeoClock® technology (Skye Pharma PLC, UK) Geoclock® tablets have an active drug inside an outer tablet layer consisting of a mixture of hydrophobic wax and brittle material in order to obtain a pH‐independent lag time prior to core drug delivery at a predetermined release rate. (PRITI P.
PEDNEKAR 2011) GeoClock® technology:
The concept is designed on the basis of Geomatrix technology. Initially a multilayer technology was recommended for constant drug release in this technology. The active core or hydrophilic matrix is coated partially on one or both bases. This partial coating adjusts the core hydration process and minimizes the surface area available for drug release. In presence of dissolution medium the barrier layer swells and becomes gel. This gelling layer is not eroded but acts as a modulating membrane to control release process. The erodible surface is instead progressively removed by the
It is hydrogel based controlled release device. This technology can provide from zero order to chronotherapeutic release. It can provide different release kinetic by manipulating molecular interactions. The authors claimed that the
“molecular engine” replaces the need for complex processing or novel excipients and allows desired drug release profiles to be “factory set” following a simple formulation development process. Basically, this technology combines primarily xanthan and locust bean gums mixed with dextrose. The physical interaction between these components works to form a strong, binding gel in the presence of water. Drug release is controlled by the rate of water penetration from the gastrointestinal tract
into the TIMERx gum matrix, which expands to form a gel and subsequently releases the active drug substance. (A. S. Mandal 2010)
8.
Marketed Technologies Of Chronopharmaceutical DDS:
Narasu4. "Formulation And Evaluation Of Chronopharmaceutical Drug Delivery Of."
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2. A. S. Mandal, N. Biswas,M.K. Kazi, A. Guha, S.
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100 3. Alessandra Maroni, Lucia Zema, Matteo Cerea,.
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49-63.
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10. Mayank Nagar, S. Singhai, V. S. Chopra, N.
Gautam, P. Trivedi2. "Chronotropic Systems; An Emerging Trend In Drug Delivery For Pulsed Release In Chronopharmacotherapy." International Journal Of Pharmaceutical And Clinical Research, 2010: 13.
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Current Reported Technologies Used In Pulsatile Drug Delivery System." International Journal Of Pharmacy Review & Research, 2012 : 23-30.
12. P. Rathee, A. Hooda, S. Rathee, V. Kumar, M.Jain. "A Biological Rhythm-Guided Approach To Drug Delivery:." International Journal Of Institutional Pharmacy And Life Sciences, 2011:
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13. Priti P. Pednekar, Chirag K. Parmar.
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An Overview." International Journal Of Current Pharmaceutical Research, 2011: 20-26.
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15. Vipul P. Patel, Tushar R. Desai2. Pharmatutor-Art-1060.
101