Overview Of Pharmaceutical Modified Release Tablet

Modified-release tablets are coated, uncoated, or matrix tablets containing excipients or prepared by procedures which, separately or together, are designed to modify the rate, the place or the time of release of the active ingredient(s) in the gastrointestinal tract. They release the medication slowly for a long time after administration of a single tablet. Used to target the site specific releases.

Modified release tablet

Comparison of blood concentration vs. time any adjuvant that can alter water uptake rate, swelling, and gelling characteristics can alter the release rate of API. The drug release can be modified by providing suitable microenvironment pH in the tablet. Inclusion of alkaline polymers results in desirable drug release of acidic drugs.

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M/R preparations may be prescribed to:

• reduce the dosing frequency and improve patient compliance;

• reduce fluctuations (peaks and troughs) in drug plasma concentrations, in order to reduce concentration-related side effects or improve effectiveness;

• control the site of drug delivery in the gastrointestinal (GI) tract.

Drugs which are absorbed only at specific sites, such as iron16, folic acid and vitamin B12, are not suitable as m/r preparations. Drugs with a long duration of action, such as amitriptyline, do not need to be given frequently and an m/r preparation is unnecessary. MR analgesic preparations with a slow onset of action are of little value when immediate pain relief is required.

Drugs with a narrow therapeutic index, those which are rapidly absorbed, and those with a short duration of action are often formulated into m/r preparations. Theophylline when prescribed for nocturnal asthma and early morning wheezing, an m/r preparation given as a single dose at night is advisable. Nifedipine m/r is better than a rapid release tablet for hypertension.

The oral controlled release formulations have been developed for those therapeutic agents that are easily absorbed from the G.I.T, having a shorter half life, eliminated quickly from the blood circulation, narrow absorption window as these will release the drug slowly into the G.I.T.

Problems can arise with the use of m/r tablets. For patients with fast GI transit time, the drug may pass site if absorption just like other types of tablet. Same way too, slow GI transit time will mean the drug will remain in a spot for long releasing its contents which can be toxic. Also, the tablet cannot be broken, crushed or chewed. One last thing is that m/r tablets can be dangerous in drug overdose.

Type Of Modified Release Tablet

Delayed-release Tablet

The drug is released at a time other than immediately after administration i.e. the site of release is controlled. They are intended to resist gastric fluid but disintegrate in intestinal fluid. This is achieved by using coating substances such as cellacefate (cellulose acetate phthalate) and anionic copolymers of methacrylic acid and its esters. It is sometimes necessary to apply more than one layer.

Extended-release Tablet

A dosage form that allows at least a twofold reduction in dosage frequency as compared to that drug presented as an immediate-release (conventional) dosage form. Examples of extended-release dosage forms include controlled-release, sustained-release, and long-acting drug products.

a. Controlled-release

the drug is released at a constant rate and plasma concentrations after administration do not vary with time.

b. Sustained Release (SR)

This is another form of modified release tablet that maintains drug release over a sustained period but not at a constant rate. The drug is released slowly at a rate governed by the delivery system. This can be achieved through a variety of formulations, including liposomes and drug-polymer conjugates (an example being hydrogels).

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List Of Abbreviations

There are several terms used interchangeably viz. controlled release, programmed release, sustained release, prolonged release, timed release, extended release etc. The most important objective for the development of these systems is to furnish an extended duration of action and thus assure greater patient compliance. Below are the list:

CD controlled delivery

CR controlled release

DR delayed release

ER extended release

IR immediate release

LA long-acting

LAR long-acting release

MR modified release

PR prolonged release

SA sustained action, short-acting

SR sustained release

TR timed release

XL extended release

XR extended release

XT extended release

Rationale For Developing Sustain Release Tablet

The following are the rationale of developing SR

1) To extend the duration of action of the drug

2) To reduce the frequency of dosing

3) To minimize the fluctuations in plasma level

4) Improved drug utilization

5) Less adverse

The performance of a drug presented as a controlled/sustained release system depends upon its:

• Release from the formulation

• Movement within the body during its passage to the site of action

The desired biopharmaceutical properties of a drug to be used in sustained drug delivery system are:

1. Drugs with good aqueous solubility are good candidate for sustained release dosage

2. The lower the molecular weight the faster and more complete will be the absorption

3. Greater the apparent partition coefficient of the drug, greater is the rate and extent of absorption

4. The drugs that exist largely in ionized form serves as poor candidates for sustained release dosage form

Drugs unstable in GI environment are poor candidates

Pharmaceutical Modification

The rate of drug release is reduced by increasing particle size or forming insoluble crystals.

Coated Pellets

Drug pellets are coated with a slowly dissolving polymer of varying thickness for varied release. The pellets can either be compressed into a tablet or put in a gelatin capsule.

Insoluble Matrix

The drug is dispersed within an insoluble porous matrix. As fluid enters the matrix, the drug is dissolved and diffuses out slowly

Eroding Matrix

The drug is dispersed within a soluble matrix. As the matrix is eroded, the drug is slowly released.

Osmotic pump

The drug and an osmotic agent are enclosed by a semipermeable membrane. As water is drawn into the tablet, dissolved drug is released in a controlled way through a laser-drilled hole.

pH Sensitive Coating

The formulation is coated with a polymer of pH dependent solubility for site specific delivery. This can either avoid drug release in the stomach (enteric coating) or specifically deliver drugs to the colon.

Advantages Of Modified Release Tablet

1. The drug release rate and site to achieve clinical objectives which cannot be attained using traditional dosage forms

2. The extended-release dosage forms can release the drug slowly upon a prolonged period by which we can reduce the frequency of dosing

3. Modified release dosage forms have less gastric irritation and side effects than immediate-release oral dosage forms

4. Modified release tablets generally come with a coating such as sugar coating, enteric coating, and film coating, and coating eliminates the unpleasant taste and odor of the drug

5. Such formulations are intended to protect the drug from the acidic medium (stomach) and allow release and absorption in the intestine

6. Coated modified-release tablets can enhance the appearance of the product and make the tablet easy to swallow for elderly and children patients.

7. It provides more precise and uniform effects of active drug ingredients (API) at particular sites.

8. Reduction of frequent doses can increase patient convenience and compliance

9. By using the modified release dosage form it is possible to reduce the risk of dose dumping and fluctuations in circulation drug levels

10. Safety margins of high potency drugs can be increased and the incidence of both local and systemic adverse side effects can be reduced in sensitive patients

11. It is possible to enhance the bioavailability with a minimum dose

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Disadvantages of modified release dosage forms

1 Their side effects may last longer than the shorter-acting, immediate release dosage forms.

2. "Cost" is another major disadvantage of extended-release dosage forms, as its formulation expensive excipients, instruments, and additional processes are required

3. If a toxic dose is in the formulation, it will remain toxic for a long time

4. Administration of modified release medication provides slower onset of action, takes a long time to produce the effect

5. The risk of dose dumping is higher in case of failed delivery of the dose, thus increased the risk of toxicity

6. It is not suitable for the drugs that absorbed at specific sites; they cannot be given in this dosage form

7. Usually, these types of pills cannot be split, need to be swallowed intact

8. Dose retrieval is difficult

9. Poor invitro and invivo correlations