Formulation of fast-opening oral tablet of amlodipine 5 mg and investigation of its physicochemical properties

Dissertation

To receive the degree of Doctor of Pharmacy

Persian Summary

Orally disintegrating tablets are solid pharmaceutical forms that open in the oral cavity in less than 1 minute without leaving a residue. The purpose of this research is to prepare and evaluate fast-opening oral tablets of amlodipine mg5, which is a long-acting blocker of calcium channels used in the treatment of chronic stable angina, vasospastic angina, and hypertension. In this study, quick-release oral tablets of amlodipine were prepared by direct compression method. In this thesis, the new auxiliary material F-Melt is used. Also, cross-carmellose sodium and sodium starch glycolate openers were used with different percentages. After conducting pre-formulation studies on the powder, we performed physicochemical control tests including diameter, thickness, weight uniformity, erosion, hardness, opening time, as well as tests to determine the amount of the effective substance and dissolution test on all formulations. Finally, the superior formulation was selected for taste evaluation. At this stage, we used different sweeteners and flavorings with different percentages, and finally the formulation with the highest taste acceptance was identified as the superior formulation. Due to the lack of this pharmaceutical form in the world market, it is hoped that we can mass produce this product in one of the domestic factories.

Key words: superdisintegrants, direct condensation, F-Melt, Avicel, magnesium stearate, mannitol, Karr index and Hasner coefficient.

. Necessity and importance of the topic

Amlodipine is a drug from the family of long-acting calcium channel blockers, which is used in the treatment of chronic stable angina, vasospastic angina, and hypertension. The way to take this medicine is orally. The oral route is easy to use. Among the oral pharmaceutical forms are tablets, which are among the most widely used pharmaceutical forms due to their ease of manufacture and good stability, as well as lower cost and easier transportation. More than 50% of the pharmaceutical forms of the market are pills. For this reason, the use of this medicinal form has a high priority. But this form of medicine also has some drawbacks. The first drawback to this form of medicine is the problem of swallowing. Some people, including children and the elderly, do not have a high swallowing ability. Also, people suffering from schizophrenia keep the pill in their mouth and do not swallow it. Also, the pill must go through several stages after swallowing. including opening, dissolving and absorption. Opening and turning into a solution form is a time-consuming process that delays the onset of the drug's effect, and from this point of view, liquid pharmaceutical forms are preferable to solid pharmaceutical forms. Due to the fact that liquid pharmaceutical forms are bulky, their use is relatively less than solid pharmaceutical forms. In recent years, the use of fast-opening oral tablets is more than in the past, these tablets have the ability to open and turn into granules after being placed in the mouth and contact with saliva, and in some cases dissolve completely. These tablets, while having the advantages of a solid form of medicine, can quickly dissolve into a suspension or solution after being placed in the mouth, and then have the advantages of liquid forms of medicine and the possibility of faster absorption of the drug and faster entry into the bloodstream and ease of swallowing for that level. Considering the swallowing problems in the elderly, the use of this medicinal form for amlodipine tablets is considered an advantage. Therefore, the aim of this thesis is to prepare amlodipine mg5 quick-release oral tablet that can release the drug quickly and also has the most suitable formulation.

1-2. Statement of the problem

The most common way of taking medicine is oral. The oral route is very easy to use and due to the large area of ??the digestive tract, it provides the possibility of wide absorption. Among the oral pharmaceutical forms are tablets, which are among the most widely used pharmaceutical forms due to their ease of manufacture and good stability, as well as lower cost and easier transportation. Pills make up more than 50% of the pharmaceutical forms in the market.For this reason, the use of this medicinal form has a high priority. One of the problems of the pill is that it causes problems for people who have swallowing problems (children and the elderly) and after swallowing the pill must go through the stages of opening, dissolution and absorption. The stage of opening and converting to a soluble form is a time-consuming process that causes a delay in the onset of the therapeutic effect, and from this point of view, liquid pharmaceutical forms are preferable to solid pharmaceutical forms. Due to the fact that liquid pharmaceutical forms are bulky, their use is relatively less than solid pharmaceutical forms, and in recent years, the use of fast-opening oral tablets has increased. These tablets have the ability to open and turn into granules after being placed in the mouth and contact with saliva, and in some cases dissolve completely, and for this reason, the digestive side effects of these medicinal systems are few (1, 2, 3). Their mechanism of action in high blood pressure (and to some extent angina) is to inhibit the entry of calcium into the arterial smooth muscle cells (3, 4).

The design of pregastric absorption systems improves the bioavailability and reduces the drug dose, and by reducing the side effects of the drug, they improve the clinical performance of the drug.

1-3. Objectives

Main objectives

Preparation of the formulation of quick-release oral tablet of amlodipine, subsequently investigating the physicochemical properties of the prepared formulations in order to achieve the final formulation, which has the desired physicochemical properties and good stability.

Objectives Sub

Investigation of the physicochemical properties of amlodipine

Preparation and various formulations of the drug amlodipine in order to obtain fast-opening tablets

Perform various physicochemical tests to evaluate the prepared formulations

Checking the taste of selected formulations in order to achieve a formulation with the desired taste

Abstract

Orally Disintegrating Tablets (ODTs) are solid dosage forms that disintegrate in the oral cavity under 1 minute leaving no residue. Amlodipine is a calcium channel blocker used in the treatment of angina and hypertension. In the present work, ODTs of Amlodipine were prepared by the direct compression method. Prior to the start of formulation studies, preliminary studies were conducted on the Amlodipine powder in order to justify its suitability for use in this study.

Results approved the suitability of powder for use. Next, formulation studies were carried out using different superdisintegrants (F-Melt, crosscarmelose sodium, crospovidone and sodium starch glycolate) with different fillers (Avicel, lactose, starch and calcium carbonate) and different lubricants (Mg Stearate, SLS and sodium benzoate).

Formulations prepared underwent different physicochemical tests. including weight variation, hardness, diameter, thickness, friability, drug content, disintegration and dissolution time.

Results showed that among different fillers, Avicel is the best. F-Melt was found to be the best providing a disintegration time of 8 seconds. The best lubricant was Mg Stearate.

Different flavoring agents were added and the mixture of menthol and sodium saccharin was found to be the best.

Finally formulation D21 containing Amlodipine, Avicel, F-Melt, Mg Stearate, Menthol, sodium saccharin and mannitol was chosen as the most desirable formulation and underwent complimentary studies including dissolution and assay.