This document discusses controlled and sustained release drug delivery systems. It defines controlled release as delivering a drug at a predetermined rate over an extended period, while sustained release aims for constant drug release but not necessarily at a predetermined rate. Controlled release offers benefits like improved compliance, consistent effects, and reduced side effects. Challenges include stability issues and increased manufacturing costs. The document then describes various approaches to controlled release, including dissolution-controlled, diffusion-controlled, and floating drug delivery systems which remain buoyant in the stomach.

1. Bholakant raut
Bachelor in Pharmacy
Quality Control Officer
Time Pharmaceuticals P. Ltd.

2.  Controlled drug delivery system is one which delivers the drug at a predetermined
rate, for locally or systematically, for a specified period of time.
 Generally controlled release (zero order Release) and sustained release (first order
release) are two terminologies which are confused with each other.
 Sustained release includes any drug delivery system that achieves constant release
of drugs over an extended period of time not particularly at a pre-determined rate.
 Controlled release includes any drug delivery system from which the drug is delivered
at a predetermined rate over a long period.
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3. Fig: Plasma drug concentration vs time plot for controlled
release, sustained release and immediate release
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4.  Improved patient compliance
 Reducing dosing frequency
 More consistent and prolonged therapeutic effect
 Reduction in health care cost
 Reducing the incidence or intensity of adverse effects and toxicity
 Better drug utilization
 Controlled rate and site of release
 Enhanced bioavailability
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5.  Stability problems
 Toxicity due to dose dumping (unintended, rapid/exaggerated drug release in short
period of time of the entire amount or significant fraction of the drug contained in a
modified release dosage form)
 Higher cost of manufacturing
 Need additional patient education and counselling
 Increased variability among dosage units, unpredictability and poor in- vitro and in-
vivo correlation
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6. 1. Dissolution controlled drug delivery system
i. Encapsulated dissolution systems
ii. Matrix dissolution systems
2. Diffusion controlled drug delivery systems
i. Reservoir devices
ii. Matrix devices
3. Dissolution and diffusion controlled systems
4. Ion exchange resins
5. PH- Independent formulation
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7. 6. Osmotically Controlled Release
7. Altered density formulation
8. Pro-drugs
9. Gastro Retentive Drug Delivery
Systems
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8. 9. GASTRO RETENTIVE DRUG
DELIVERY SYSTEMS (GRDD)
 Oral delivery of drugs is by far the most preferable route of drug delivery due to the
ease of administration, low cost of therapy and patient compliance.
 Complicated by limited gastric residence times
 Rapid GI transit can prevent complete drug release in the absorption zone and reduce
the efficacy of the administered dose since the majority of drugs are absorb in
stomach or the upper part of small intestine.
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10. A number of systems have been pursued to increase the gastric residence time of dosage forms by
employing a variety of concepts. These systems have been classified according to the basic
principles of gastric retention. They are
1. Floating Drug Delivery System (FDDS), with low density providing sufficient
buoyancy to float over the gastric contents.
2. Bioadhesive systems, enabling the localized retention of the system in the stomach.
3. Swelling and expanding systems, preventing transit from the gastric sphincter.
4. High density systems, remaining in the stomach for longer period of time, by sedimenting to
the folds of stomach.
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12.  Floating systems or hydrodynamically controlled systems are low-density systems that
have sufficient buoyancy to float over the gastric contents and remain buoyant in the
stomach without affecting the gastric emptying rate for a prolonged period of time.
 While the system is floating on the gastric contents, the drug is released slowly at the
desired rate from the system.
 After release of drug, the residual system is emptied from the stomach.
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13. Based on the mechanism of floating, the floating drug delivery system are of 2 type:
A. Non- effervescent and
i. Colloidal gel barrier systems
ii. Microporous compartment systems
iii. Alginate beads etc.
B. Effervescent drug delivery system.
i. VOLATILE LIQUID CONTAING SYSTEM
ii. GAS GENERATING SYSTEM
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14. Non-effervescent floating dosage forms use a gel forming or swellable cellulose type
hydrocolloids, polysaccharides, and matrix-forming polymers like polycarbonate,
polyacrylate, polymethacrylate, and polystyrene.
The formulation method includes a simple approach of thoroughly mixing the drug and
the gel-forming hydrocolloid.
After oral administration, this dosage form swells in contact with gastric fluids and
attains a bulk density of < 1.
The air entrapped within the swollen matrix imparts buoyancy to the dosage form.
The so formed swollen gel-like structure acts as a reservoir and allows sustained
release of drug through the gelatinous mass.
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15. i. Volatile liquid containing systems:
These have an inflatable chamber which contains a volatile liquid e.g. ether,
cyclopentane, that evaporates at body temperature to cause the inflation of the
chamber in the stomach. These systems are osmotically controlled floating systems
containing a hollow deformable unit. There are two chambers in the system, first
contains the drug and the second chamber contains the volatile liquid.
ii. Gas generating systems:
These buoyant delivery systems utilize effervescent reaction between
carbonate/bicarbonate salts and citric/tartaric acid to liberate CO2, which gets
entrapped in the jellified hydrocolloid layer of the system, thus decreasing its specific
gravity and making it floats over chime.
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