## 1 Introduction  
Preformulation studies provide important information on active ingredients and are useful for developing new drug delivery systems, for the selection of the excipients, pharmaceutical technology and process parameters to ensure the quality and stability of the final product and in vivo behaviour [1; 2; 3]. Preformulation studies focus on the physical and chemical properties of the active ingredient which could affect its performance and the development of a prolonged-release dosage form. The formulation considerations are also essential for achieving a pharmaceutical form suitable for commercial use and for administration to humans. According to the World Health Statistics 2019 report released in Geneva in August 2021, the number of adults suffering from raised blood pressure has increased from 650 million to 1.28 billion in the last thirty years. Hypertension is a condition that causes around half of all deaths from stroke and heart disease. About 53% of women and 62% of men with hypertension, or a total of 720 million people, were not taking any medication, even though there is clear evidence that the medicines are effective in bringing blood pressure into the normal range [4]. In the early 1970s, a new class of calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists, dihydropyridines (nifedipine, amlodipine, felodipine, nimodipine) was discovered and introduced in the therapy of high blood pressure [5]. Currently, dihydropyridine (DHP) calcium channel blockers are often used to reduce systemic vascular resistance and arterial pressure. Sometimes when they are used to treat angina, the vasodilation and hypotension can lead to reflex tachycardia, which can be detrimental to patients with ischemic symptoms because of the resulting increase in myocardial oxygen demand. Calcium channel blockers prevent the opening of calcium channels and thereby reduce the concentration of intracellular calcium. They mainly affect arterial vascular smooth muscle and lower blood pressure by causing vasodilation [6]. For the present study, felodipine was selected as an active ingredient for extended-release tablets. Felodipine has the advantages of being more selective as a vasodilator and having fewer cardiac effects than other calcium antagonists, but it has poor bioavailability of only 15% after oral administration [7]. Felodipine (ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate) (Scheme 1), along with other substituted dihydropyridine compounds, is a class II drug according to the Biopharmaceuous Classification System, with low water solubility (around 3 \(\mu\)g/mL) and high permeability [8; 9; 10]. Ingredients with low water solubility cause formulation problems due to their reduced dissolution rate in aqueous media, and therefore in the gastrointestinal tract. These characteristics result in low absorption of the therapeutically active substance, thus having a reduced bioavailability after oral administration. Furthermore, the bioavailability of felodipine decreases with the effect of the first hepatic passage [11]. To ensure optimal felodipine absorption, the composition of the solid oral pharmaceutical form must provide an extended release profile that provides therapeutic plasma concentrations for a duration of about 10-12 h.  
Extended release is preferable in the case of drugs that require repeated, long-term and high-frequency administration due to their short half-life [12]. An immediate-release formulation could cause fluctuations in hemodynamic effects due to repeated administration at short intervals. Reducing plasma concentrations of the drug before the next dose, most often in the morning, result in reduced blood pressure control in the patients, with large effect variations.