Development and Evaluation of Sublingual Tablet of Lercanidipine by Solid Dispersion Method

Abstract

The purpose of this study was to develop and evaluate a sublingual tablet of lercanidipine hydrochloride for the direct compression method of treating hypertension by using a solid dispersion technique. The dihydropyridine calcium-channel blocker lercanidipine Hydrochloride is used to treat hypertension, Prinz metal’s variant angina, and chronic stable angina pectoris. It can be administered alone or in combination with an angiotensin-converting enzyme inhibitor. The biological half-life of lercanidipine hydrochloride is 8–10hours, and its duration of action is up to 24hours. Because of its first pass metabolism, lercanidipine hydrochloride has a less than 10% oral bioavailability. BCS class II was applied to lercanidipine hydrochloride due to its high permeability and poor solubility. The aforementioned features and attributes render Lercanidipine Hydrochloride a fitting contender for a sublingual tablet created by robust dispersion and integrating Gelucire 50/13. When compared to pure lercanidipine Hydrochloride, the solubility is high when Gelucire 50/13 was used at the highest concentration. This is the first attempt to improve the solubility of pure lercanidipine HCl free base by the use of various solid dispersion methods, including solvent evaporation, fusion, and physical mixing. Lercanidipine HCl kneading solid dispersion, made with Gelucire 50/13 (1:1)., The prepared lercanidipine HCl sublingual tablets prevent first pass metabolism, avoid swallowing-related issues, particularly in elderly patients, and enhance solubility. The tablet disintegrated in 50 seconds, according to the results. Similarly, a dissolution study conducted in vitro revealed 96.68% drug release in 10 minutes. The prepared lercanidipine HCl sublingual tablets containing a complex with Gelucire 50/13 solid dispersion were found to significantly improve patient compliance and bioavailability.

Introduction

Hypertension, a medical disorder characterized by chronically raised blood pressure in the arteries, is sometimes referred to as high blood pressure 1,2. While the WHO uses the value 160/95mm Hg, the American Heart Association defines hypertension as an arterial blood pressure value greater than 140/90 mm Hg. Systolic and diastolic blood pressure readings are obtained 3. In order to determine the risk of heart disease, both measurements are crucial. Hypertension is defined as a consistent diastolic blood pressure of more than 90mm Hg accompanied by a rise in the systolic blood pressure to more than 140mm Hg. An abnormally high blood pressure is caused by an increase in peripheral vascular smooth muscle tone, which also causes an increase in arteriolar resistance and a decrease in the venous system’s capacitance 4-6.

Primary and secondary hypertension, which are categorized based on factors like age, family history, and being less physically active, Being overweight or obese, smoking cigarettes, High salt consumption, Less potassium intake, Heavy drinking of alcohol, Stress and Chronic illnesses like diabetes and renal failure 7. Hypertension is rarely accompanied by symptoms, some persons with high blood pressure describe headaches, as well as light headedness, vertigo, tinnitus, impaired vision or episodes.

When a medication is administered sublingually, it is inserted beneath the tongue and enters the bloodstream through the floor of the mouth and the tongue’s ventral surface8. When no fluids or water are consumed, the fast- dissolving tablet format is intended to allow the administration of an oral solid dose form. Usually, just the saliva in the buccal cavity is sufficient to dissolve these tablets 9-10.

With an almost 100% bioavailability and a 3–7-hour elimination half-life, oral absorption is quick, homogeneous, and thorough. Thus, the goal of the New Drug Delivery Systems is to improve patient compliance by creating a dose form that is easy to deliver 11.

Consequently, oral mucosal drug delivery has become more popular as a substitute system drug delivery technique that has a number of benefits over injectable and internal delivery methods that have the same effect as intravenous routes 12-13.

A calcium channel blocker called lercanidipine hydrochloride was first made available to treat hypertension. Its first pass metabolism occurs in the gut wall and liver, and its oral bioavailability is 10% 14-15. The sublingual dosage form provides a quicker release of the medication into the bloodstream, avoiding the liver’s metabolism of nifedipine and providing quicker and more effective relief from hypertension and anginal discomfort.

Solid dispersion is defined as the dispersion of one or more active ingredients in an inert carrier that has been created utilizing various solid dispersion technology techniques while it is in a solid form. The medication is released at the point where the solid dispersion and aqueous medium come into contact by a hydrophilic inert carrier 16-17.

Gelucire 50/13 carrier is a highly crucial and significant factor in particle wettability; if wettability is good, solubility will naturally increase, which will enhance bioavailability. Gelucire 50/13 carrier is a highly crucial and significant factor in particle wettability; if wettability is good, solubility will naturally increase, which will enhance bioavailability 18.

In lipid-based formulations, Gelucire 50/13 is a non-ionic water-dispersible surfactant that improves the oral bioavailability of weakly water-soluble APIs by solubilizing them. In aqueous media, it self-emulsifies to form a fine dispersion 19. The two primary functions of the bioavailability enhancer and solubilizer are for poorly soluble APIs.

There are various methods for creating the sublingual tablets, but the direct compression approach is the most practical since it just calls for adding a lercanidipine hydrochloride Gelucire 50/13 solid dispersion to the mixture. For pharmaceuticals that are sensitive to heat or moisture, direct compression is the best option since it eliminates the need for heat or water during the formulation process 20.

In this study, a direct compression method was employed to analyze the sublingual lercanidipine hydrochloride tablets using the Gelucire 50/13 solid dispersion. Numerous metrics, such as bulk density, tapped density, hardness, friability, in vitro disintegration, and dissolving time tests, were used to assess the quality of the formulations 21.

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Materials

Lercanidipine hydrochloride was obtained as a gift sample from CTX Life Sciences Pvt. Ltd., Surat, India. Gelucire 50/13 was obtained as a gift sample from Gattefosse SAS, India. Vishal Chem, Mumbai, India provided D-mannitol, D- sorbitol, Avicel Ph 101, Avicel Ph 102, Crospovidone, Sodium starch glycolate, Cross Carmellose Sodium, Polyvinyl povidone K-30, Methanol, Magnesium stearate, and Talc. Analytical grade solvents and chemicals were used only.

Table No. 1: Formulations from F1 to F6 ^23-25

Anuradha Prajapati, Patel Mehulkumar Pramodbhai, Shruti Jagdish Patel, Soniya Remeshing Sharan, Abhishek Shivshankar Shukla, Kriti Rajesh Singh, Shailesh Luhar, Sachin Narkhede. Development and Evaluation of Sublingual Tablet of Lercanidipine by Solid Dispersion Method. Research Journal of Pharmaceutical Dosage Forms and Technology. 2025; 17(2):91-6. doi: 10.52711/0975-4377.2025.00013

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