The reason behind different formulations of the same medication

Assortment of pills and capsules

Assortment of pills and capsules

Mr Pharmacist, I have high blood pressure. I have been on Nifedipine for sometime now. Recently I was changed from this Nifedipine (retard) to this other one (Nifedipine XL). Kindly explain the difference thoroughly to me. The first one is Nifedipine tablets 20mg retard which you were taking twice daily (every 12 hours).

This second one is Nifedipine tablets XL 30mg which you are now required to take once a day. The XL means extended release. Nifedipine tablet/capsule ordinarily is a short acting with a half life (or duration of action) of 2 to 5 hours. This would have required three times dosing (8 hourly) for blood pressure control over 24 hour period.

An attribute of good antihypertensive drug is its ability to lower blood pressure (BP) smoothly throughout the day and night. This is usually evaluated by estimating the trough to peak (T/P) ratio. The trough is the BP reduction at the end of each dosing period, measured just before the next dose of medication is taken. The peak is the maximal BP reduction recorded after taking the medication. It is desirable to have a T/P ratio of at least 60 per cent (USA FDA guidelines puts the figure at 50per cent). The closer the T/P ratio is to 100 per cent the smoother the BP control over 24 hours.

The trough:peak ratio is therefore an indicator of the efficacy of the antihypertensive in its BP lowering effect over 24 hours. A high trough:peak ratio reflects a balanced and durable anti hypertensive effect and protects the patient against medication induced blood pressure fluctuations. The trough:peak ratio provides an index of how well the anti hypertensive effect is sustained over the dose interval. Furthermore, Nifedipine is a dihydropyridine calcium channel blocking agent with its blood pressure lowering effect primarily due to its vasodilatory action.

The most common adverse effects of Nifedipine such as dizziness, flushing, headache, palpitation are more pronounced in the ordinary short acting tablet/capsule formulation.

These reasons account for the various modified release formulations of Nifedipine. Drug products are sometimes designed to reduce the frequency of dosing by modifying the rate of drug absorption. Many terms are used to describe modified release products. These include extended release, prolonged release, controlled release, controlled delivery, slow release, sustained release, long acting, and delayed release. A delayed release medication releases the drug at a time other than immediately following administration.

The first modified release formulation of Nifedipine is the retard which has a duration of action of about 12 hours. This explains why it is dosed twice daily (12 hourly). Taking the retard Nifedipine once a day leaves you about 12 hours not covered by the antihypertensive. It means that if you have high blood pressure and on Nifedipine retard 10mg or 20mg tablet once daily then your blood pressure reduction will only occur over 12 hours instead of the required 24 hour blood pressure control.

This explains why Nifedipine retard is dosed twice daily (12 hourly). There is then the extended release formulation as seen in Nifedipine tablet XL formulations. This prolongs the duration of action of Nifedipine over a 24 hour. The long acting formulations release the active ingredient in bits over a longer period of time and thus minimizes the associated adverse effects of Nifedipine. In this regard the extended release formulations (XL) are better than the retard in the incidence of side effects.

Other benefits are sustained blood levels and improved patient compliance especially in the elderly. As regards the Nifedipine retard 20mg twice (12 hourly) being converted to the Nifedipine XL 30mg it means that your health care provider considers your blood pressure at a level that can still be adequately controlled with the XL 30mg formulation. It is important to stress the problems associated with modified release formulations. Such formulations (particularly the extended release ones) contain a higher drug load (e.g. Nifedipine LA 60mg) and thus any loss of integrity of the release characteristics of the dosage form could be dangerous. Modified release formulations should not be crushed or chewed as the slow release characteristics would be lost and rather cause toxicity.

There are some newer modified release preparations that could be divided to provide half doses but modified release formulations should generally be taken whole. Some persons also prefer putting tablets into water to dissolve before swallowing.

Modified release preparations cannot be crushed or dissolved in water before swallowing. Such an action quickly converts the modified release formulation into a short acting Nifedipine. The blood pressure can be very profound and dangerous to the patient. It is important to stick to the same modified release formulation.

Different versions of modified release preparations may not have the same clinical effect (BNF 68 Calcium channel blockers). As I write this piece, the 75th Congress of the International Pharmaceutical Federation (FIP) is underway in Düsseldorf, Germany with the theme “Better practice science based, evidence driven”. Modified release formulations as applied to various dosage forms of Nifedipine is a clear example of better practice in the management of high blood pressure based on science and driven by evidence of effectiveness.

By Edward  O. Amporful

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