SUSTAINED RELEASE DRUG DELIVERY SYSTEM : A CONCISE REVIEW
Figure 7. Diagrammatic representation of Ion Exchange resins.
Swelling and Expansion Systems
Conventional hydrogels swell slowly upon contact with water due to their small pore size, which usually ranges in the nanometers and low-micrometer scale. However if the hydrogel has a pore size of more than 100 µm, swelling is much faster and may lead to a large increase in size. Swelling ratios of over 100 can be achieved. These swollen systems become too large to pass through the pylorus and thus may be retained in the stomach even after housekeeper wave, provided they have a sufficiently high mechanical strength to withstand the peristaltic movement in the antrum of the stomach.
Figure 8. Diagrammatic representation of Swellingand Expansion Systems.
If the dosage form has a lower density than the gastric fluids, it will float on a top of the stomach content, allowing for an increased time span to release the drug before the system is emptied out into small intestine. The gastric fluid has a density of approximately 1gm/cm3. If the density of the dosage form is lower than that, it will float on the gastric fluids. These systems require the presence of sufficient fluid in the stomach and the presence of food as discussed above. Several types of low density ingle-unit dosage forms (tablets) and multiple-unit dosage forms (pellets) have been developed. If a dosage form has density of larger than approximately 2.5gm/cm3, it will sink to the bottom of the stomach and pellets may be trapped in the folds of the gastric wall.
Figure 9. Diagrammatic representation of Floating Systems
Bioadhesive or Mucoadhesive Systems
It has also been suggested to use Bioadhesive or Mucoadhesive polymers such as polyacrylic acid and chitosen to achieve gastric retention. The basic idea here is that the mucoadhesive or bioadhesive polymers leads to the dosage forms sticking on to the mucus of the gastric wall. Whilst the bioadhesive or mucoadhesive approach is a sensible one for buccal or sublingual formulations, due to rapid turnover of the mucus in the stomach, for gastroretentive systems this approach is not as straightforward. Finally magnetic materials may be added to the dosage forms. These systems can then be held in place by an external magnate, but this approach requires a precise positioning of the external magnate and is not likely to have a high patient compliance.
Figure 10. Diagrammatic representation of Bioadhesiveor Mucoadhesive systems.
One of the least complicated approaches to the manufacture of sustained release dosage forms involves the direct compression of blends of drug, retardant materials and additives to form a tablet in which drug is embedded in matrix core of the retardant. Alternately, retardant drug blends may be granulated prior to compression.
TYPES OF MATRIX
In this method of obtaining sustained release from an oral dosage form, drug is mixed with an inert or hydrophobic polymer and then compressed in to a tablet. Sustained release is produced due to the fact that the dissolving drug has diffused through a network of channels that exist between compacted polymer particles. Examples of materials that have been used as inert or hydrophobic matrices include polyethylene, polyvinyl chloride, ethyl cellulose and acrylate polymers and their copolymers.
These matrices prepared by the lipid waxes and related materials. Drug release from such matrices occurs through both pore diffusion and erosion. Release characteristics are therefore more sensitive to digestive fluid composition than to totally insoluble polymer matrix. Carnauba wax in combination with stearyl alcohol or stearic acid has been utilized for retardant base for many sustained release formulation.
A matrix is defined as well mixed composite of one or more drugs with a gelling agent (hydrophilic polymer). These systems are called swellable controlled release systems. The polymers used in the preparation of hydrophilic matrices are divided in to three broad groups,
A. Cellulose derivatives:Methylcellulose 400 and 4000cPs, Hydroxyethylcellulose; Hydroxypropylmethylcellulose (HPMC) 25, 100, 4000 and 15000cPs; and Sodium carboxymethylcellulose.
B. Non cellulose natural or semi synthetic polymers:Agar-Agar; Carob gum; Alginates; Molasses; Polysaccharides of mannose and galactose, chitosan and modified starches.
These consist of the polymers which comprised of monomers linked to one another through functional groups and have unstable linkage in the backbone. They are biologically degraded or eroded by enzymes generated by surrounding living cells or by nonenzymetic process in to oligomers and monomers that can be metabolized or excreted. Examples are natural polymers such as proteins and polysaccharides; modified natural polymers; synthetic polymers such as aliphatic poly (esters) and poly anhydrides.
These consist of polymers which are obtained from various species of seaweeds. Example is Alginic acid which is a hydrophilic carbohydrate obtained from species of brown seaweeds (Phaephyceae) by the use of dilute alkali.
On the Basis of Porosity of Matrix: Matrix tablets can be divided in to 3 types.
· Macro porous Systems: In such systems the diffusion of drug occurs through pores of matrix, which are of size range 0.1 to 1 μm. This pore size is larger than diffusant molecule size.
· Micro porous System: Diffusion in this type of system occurs essentially through pores. For micro porous systems, pore size ranges between 50 – 200 A°, which is slightly larger than diffusant molecules size.
· Non-porous System: Non-porous systems have no pores and the molecules diffuse through the network meshes. In this case, only the polymeric phase exists and no pore phase is present.
MASRx AND COSRx SUSTAINED-RELEASE TECHNOLOGY13, 14, 15
The objective is to assess factors affecting drug release from guar-gum-based once-daily matrix sustained-release formulations (MASRx). The tablets were designed to hydrate completely into the tablet core. In the process, the tablet core expanded and released the drug in a sustained-release manner.
Formulations base on constant sustained-release matrix (COSRx) technology can also be developed using guar gum as a major rate-controlling polymeric material. Depending on the solubility of the drug, low- or high-viscosity guar gum can be use. The formulation involves a guar-gum-base tablet and a combination of water-soluble and water-insoluble polymeric tablet coat. When the tablet is placed in a dissolution medium, there is slow diffusion of water through the polymeric wall leading to swelling and gelations of the guar gum/drug core. As the hydration a progress, the tablet continues to swell until the wall breaks, forming a sandwich-like structure. The release of drug proceeds primarily out of the sides of the tablet as it passes through the intestinal tract. The tablets provide a nearly zero-order drug release following a programmed period of delayed drug release.
DRUG RELEASE MECHANISM FROM MATRIX SYSTEMS16, 17, 18
Zero Order Kinetics
A zero order release would be predicted by the following equation,
Qt - Q0 = K0t
Where, Qt = Amount of drug release dissolved in time‘t’.
Qo = Initial amount of drug concentration in solution.
K0t = Zero order rate constant.
When the data was plotted as cumulative % drug release verses time, if the plot is linear then data obeys zero order kinetics with slope equal to Ko. This model represents an ideal release profile in order to achieve the prolonged pharmacological action.
First Order Kinetics
A first order release would be predicted by the following equation
Log Qt = Log Qo - K1t/2.303
Where, Qt = Amount of drug released in time‘t’.
Qo = Initial amount of drug concentration in solution.
K1t = First order rate constant.
When data was plotted as log cumulative % drug remaining verses time yields a straight line indicating that the release follows first order kinetics. The constant K can be obtained multiplying slope values.
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