Dissolution Studies Research Articles

Dissolving microarray patches loaded with a rotigotine nanosuspension: A potential alternative to Neupro® patch

Parkinson's disease (PD), affecting about ten million people globally, presents a significant health challenge. Rotigotine (RTG), a dopamine agonist, is currently administered as a transdermal patch (Neupro®) for PD treatment, but the daily application can be burdensome and cause skin irritation. This study introduces a combinatorial approach of dissolving microarray patch (MAP) and nanosuspension (NS) for the transdermal delivery of RTG, offering an alternative to Neupro®. The RTG-NS was formulated using a miniaturized media milling method, resulting in a nano-formulation with a mean particle size of 274.09 ± 7.43 nm, a PDI of 0.17 ± 0.04 and a zeta potential of −15.24 ± 2.86 mV. The in vitro dissolution study revealed an enhanced dissolution rate of the RTG-NS in comparison to the coarse RTG powder, under sink condition. The RTG-NS MAPs, containing a drug layer and a ‘drug-free’ supporting baseplate, have a drug content of 3.06 ± 0.15 mg/0.5 cm2 and demonstrated greater amount of drug delivered per unit area (∼0.52 mg/0.5 cm2) than Neupro® (∼0.20 mg/1 cm2) in an ex vivo Franz cell study using full-thickness neonatal porcine skin. The in vivo pharmacokinetic studies demonstrated that RTG-NS MAPs, though smaller (2 cm2 for dissolving MAPs and 6 cm2 for Neupro®), delivered drug levels comparable to Neupro®, indicating higher efficiency per unit area. This could potentially avoid unnecessarily high plasma levels after the next dose at 24 h, highlighting the benefits of dissolving MAPs over conventional transdermal patches in PD treatment.

Iron Chelation in Soil: Scalable Biotechnology for Accelerating Carbon Dioxide Removal by Enhanced Rock Weathering.

Enhanced rock weathering (EW) is an emerging atmospheric carbon dioxide removal (CDR) strategy being scaled up by the commercial sector. Here, we combine multiomics analyses of belowground microbiomes, laboratory-based dissolution studies, and incubation investigations of soils from field EW trials to build the case for manipulating iron chelators in soil to increase EW efficiency and lower costs. Microbial siderophores are high-affinity, highly selective iron (Fe) chelators that enhance the uptake of Fe from soil minerals into cells. Applying RNA-seq metatranscriptomics and shotgun metagenomics to soils and basalt grains from EW field trials revealed that microbial communities on basalt grains significantly upregulate siderophore biosynthesis gene expression relative to microbiomes of the surrounding soil. Separate in vitro laboratory incubation studies showed that micromolar solutions of siderophores and high-affinity synthetic chelator (ethylenediamine-N,N'-bis-2-hydroxyphenylacetic acid, EDDHA) accelerate EW to increase CDR rates. Building on these findings, we develop a potential biotechnology pathway for accelerating EW using the synthetic Fe-chelator EDDHA that is commonly used in agronomy to alleviate the Fe deficiency in high pH soils. Incubation of EW field trial soils with potassium-EDDHA solutions increased potential CDR rates by up to 2.5-fold by promoting the abiotic dissolution of basalt and upregulating microbial siderophore production to further accelerate weathering reactions. Moreover, EDDHA may alleviate potential Fe limitation of crops due to rising soil pH with EW over time. Initial cost-benefit analysis suggests potassium-EDDHA could lower EW-CDR costs by up to U.S. $77 t CO2 ha-1 to improve EW's competitiveness relative to other CDR strategies.

Formulation, design, and evaluation of valsartan sodium-sustained-release matrix tablets

The main aim of present work was to formulate and evaluate sustain release matrix tablets of Valsartan, an angiotensin II Receptor type 1 antagonist. Sustain release formulation are those which delivers the drug locally or systemically at a predetermined rate for a fixed period of time. The matrix tablet was prepared by direct compression method using by various concentration of chitosan and sodium alginate with combination of various release retardant polymer. The powder mixtures were subjected to various pre-compression parameters such as angle of repose, bulk density, tapped density and Carr’s index shows satisfactory result and the compressed tablets are evaluated for post-compression parameters such as weight variation, thickness, hardness, friability, drug content, in-vitro dissolution and stability studies. In-vitro dissolution studies were carried out for 24 hours using 0.1N HCl for first 2 hours and pH 6.8 phosphate buffers for 24 hours and the result showed that formulations F4 and F7 showed good dissolution profile to control the drug release respectively. Formulation containing higher concentration of chitosan and sodium alginate along with polymers sustainedthedrugreleasefor theperiodof24hours.The compatibilityof thedrug, polymers and other excipients were determined by FT-IR Spectroscopy. Results showed that the drug was compatible with polymers and other excipients. The release data was fitted to various mathematical models such as Zero-order, First-order, Higuchi equation and Korsmeyer- Peppas model to evaluate the kinetics and the drug release. The drug release followed first order and the mechanism was found to be non-Fickian. The stability studies were carried out for 3 months and result indicates that the selected formulations (F4and F7) were stable.

In-Vitro Dissolution Study of Solid Dispersion Adsorbate of Nateglinide by Eco-Friendly Liquid Chromatography-Tandem Mass Spectrometric Method through Harmonized Approach of White Analytical Chemistry and Analytical Quality by Design

In-Vitro Dissolution Study of Solid Dispersion Adsorbate of Nateglinide by Eco-Friendly Liquid Chromatography-Tandem Mass Spectrometric Method through Harmonized Approach of White Analytical Chemistry and Analytical Quality by Design

Effect of postprandial gastric conditions on in vitro drug release from modified release mesalamine formulations

The effect of gastric prandial conditions on in vitro drug release from oral, locally acting, colon-targeted, mesalamine formulations has not been previously evaluated. In vitro dissolution of four mesalamine formulations were investigated using a USP II paddle apparatus. Fed gastric conditions were simulated under three consecutive phases of milk/buffer at different ratios to simulate changes in physicochemical, gastric composition during food digestion. Drug release was not observed from enteric coated preparations in the fasted state. Under simulative postprandial gastric conditions, however, drug release from Apriso® extended release (ER) capsules was 19 ± 4.7 %. As for Lialda® delayed release (DR) tablets, following two hours of exposure to simulative ileo-colonic media comprising bicarbonate buffer, drug release in the fed and fasted states was 55.7 ± 22.4 % and 12.4 ± 6.4 %, respectively. Significant differences in in vitro dissolution profiles were not observed between fasted and fed conditions for Pentasa® ER capsules and Asacol® HD DR tablets. Published pharmacokinetic data for Apriso and Lialda show higher systemic absorption of mesalamine in fed compared to fasted individuals. Our in vitro data is consistent with these pharmacokinetic findings since fed conditions may give rise to a higher extent of proximal drug release and therefore greater systemic absorption. Furthermore, extent of systemic exposure to mesalamine from Pentasa and Asacol was found not to be affected by food intake. In vitro dissolution studies simulating the gastric prandial state can possibly predict the impact of food on drug release from delayed and sustained release, locally acting formulations.

FORMULATION AND EVALUATION OF LOSARTAN POTASSIUM MATRIX TABLETS BY USING DIFFERENT POLYMERS

The study aims to create a sustained release matrix tablet for Losartan potassium, an angiotensin II receptor antagonist, to improve patient compliance and maintain therapeutic blood or tissue levels for extended periods. The research investigates the role of novel semi-synthetic polymers and natural polymers in comparison to well-known release retarding agents. Gastroretentive drug delivery systems (GRDDS) are unique technologies designed to improve drug bioavailability and absorption by avoiding the first-pass effect. Losartan potassium, an angiotensin II receptor antagonist, has a bioavailability of 32% and a low elimination half-life, making it suitable for oral controlled release. The study utilized natural and synthetic polymers in matrix tablet preparation, concentration, drug particles size, additives, and excipients to modify drug release. The powder mixtures were tested for pre-compression parameters and post-compression parameters, and in-vitro dissolution studies showed good dissolution profiles for drug release. Formulations with higher concentrations and polymers sustained drug release for 24 hours. FT-IR Spectroscopy confirmed drug compatibility with polymers and other excipients KEYWORDS: matrix tablets, Losartan Potassium, flow properties, pre compression parameters post compression parameters, In-vitro dissolution.

Eutectic mixtures containing the active pharmaceutical ingredient ezetimibe: Phase diagrams, solid state characterization and dissolution profiles

Cardiovascular disease represents the leading cause of death worldwide, according to the World Health Organization (WHO) report. One of the treatment strategies is the use of the drug ezetimibe (EZT). This drug is a cholesterol absorption inhibitor with low aqueous solubility, which affects its therapeutic efficacy. The purpose of this paper was to obtain eutectic materials of EZT with methylparaben (MPB), salicylic acid (SCA) and nicotinamide (NTM) coformers, and to study their phase diagrams, dissolution properties and hygroscopicity to assess possible enhancements. Phase and Tamman diagrams were constructed using differential scanning calorimetry (DSC) results. The eutectic materials were characterized by powder X-ray diffraction (PXRD) and polarized light optical microscopy (OM). The hygroscopicity of the materials was assessed at different relative humidities (RH) through dynamic vapor sorption (DVS). The dissolution study was conducted with the materials in powder form, with paddle dissolution, rotating at 50 rpm, in 900 mL of aqueous buffer solution at pH 6.8 and 37 °C. The phase diagrams demonstrated that EZT formed eutectic systems with eutectic molar fractions of 0.59, 0.67 and 0.69 for EZT-SCA, EZT-NTM and EZT-MPB, respectively. The three eutectic materials are characterized as microcrystalline conglomerates of their components. In terms of the hygroscopic behavior of EZT at different RHs, eutectic materials demonstrated lower susceptibility to monohydrate formation compared to the anhydrous form. In dissolution studies, EZT-SCA and EZT-MPB solubilized EZT in amounts 22 % higher than the pure drug in 15 min. On the other hand, EZT-NTM eutectic suppressed the dissolution of EZT down to 56 % at the same time. The results indicated the possibility of obtaining materials with enhanced properties using eutectic mixtures, with improved dissolution rates and hygroscopic stability.

A Better Method for Pharmaceutical Quality Control for Impurity Profile Data

The objective of present investigation was to design the concept of hydro dynamically balanced bilayered tablet containing glimepiride and pioglitazone hydrochloride as immediate release layer and metformin hydrochloride as sustain release floating layer. Floating layer of metformin hydrochloride was prepared by employing different grades of gel forming agent and by various gas generating agent. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy, swelling index and dissolution studies. The prepared tablets exhibited satisfactory physico-chemical characteristics. All the prepared batches showed good in vitro buoyancy. The tablet swelled radially and axially during in vitro buoyancy studies. It was observed that the tablet remained buoyant for 12 hours. The drug release from the tablets was sufficiently sustained.

Long-Term Physical Stability of Amorphous Solid Dispersions: Comparison of Detection Powers of Common Evaluation Methods for Spray-Dried and Hot-Melt Extruded Formulations

Although physical stability can be a critical issue during the development of amorphous solid dispersions (ASDs), there are no established protocols to predict/detect their physical stability. In this study, we have prepared fenofibrate ASDs using two representative manufacturing methods, hot-melt extrusion and spray-drying, to investigate their physical stability for one year. Intentionally unstable ASDs were designed to compare the detection power of each evaluation method, including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and dissolution study. Each method did not provide the same judgment results on physical stability in some cases because of their different evaluation principles and sensitivity, which has been well-comprehended only for one-component glass. This study revealed that the detection powers of each evaluation method significantly depended on the manufacturing methods. DSC was an effective method to detect a small amount of crystals for both types of ASDs in a quantitative manner. Although the sensitivity of XRPD was always lower compared to that of DSC, interpretation of the data was the easiest. SEM was very effective for observing the crystallization of the small amount of drug for hot-melt extruded products, as the drug crystal vividly appeared on the large grains. The dissolution performance of spray-dried products could change even without any indication of physical change including crystallization. The advantage/disadvantage and complemental roles of each evaluation method are discussed for deeper understanding on the physical stability data of ASDs.

Quantitative study on the metal dissolution reaction with multivalent cations by a modified SECM mode: Pure Ti as a case

Metal corrosion exhibits coupled multi-reaction features, making it challenging to quantitatively study the dissolution reaction with variable-valent cations, particularly in valence quantification. This work develops a novel scanning electrochemical microscopy mode and applies it to Ti dissolution study in acidic fluorides. This mode identifies the potential-dependent corrosion reactions and quantifies the valence evolution of Ti from HER to transpassive regions. Results provide direct electrochemical evidence for soluble Ti(z≤3), for the first time, and revise the reported dissolution equation. The proposed mode overcomes the drawbacks of macro-electrochemical analysis based on coupling information and provides an effective quantitation method for anodic reactions.

Formulation and evaluation of emulgels loaded with microspheres containing Baricitinib

The main objective of the present research work was to formulate and evaluate transdermal gel loaded with microspheres of Baricitinib to increase bioavailability and to reduce the dosing frequency and to improve patient compliance. Gel loaded with microspheres of Baricitinib was prepared by taking different ratios and grades of Carbopol polymers. The prepared formulations (F1–F9) were evaluated for pre-formulation studies, percentage yield, particle size, content Uniformity, drug content entrapment efficiency and in vitro dissolution studies. The optimized gel loaded with microspheres of F8 formulation (drug: Carbopol 974polymer in 1:1 ratio) is more effective compared to all formulations. The prepared gel showed acceptable physical properties such as particle size of (126.5 microns), percentage yield of (96.5%), content uniformity (97.8), and drug content entrapment efficiency (90.5%). In vitro dissolution studies have shown 100.1% drug release in 12 h. With the optimized formulation Baricitinib emulgels are formulated using different grades and ratios of Carbopol and optimized microsphere formulation F8. The Emulgel formulation F7 showed the acceptable results with a yield of 92.3%, Drug content (100.2%), Spread ability (13.38 g.cm/s), Viscocity (112.3 cP), pH off 6.05 and it was observed that formulation F7 showed 100.2% drug release within 12 hours. All the results show that the gel loaded with microspheres of Baricitinib can be effectively used for the treatment of viral infections like small fox.

Effect of White Rice Flour in the Formulation Development and Evaluation of Sumatriptan Succinate Floating Microspheres by Modified Emulsion Solvent Diffusion Method

A sustained release system for Sumatriptan designed to increase its residence time in the stomach without contact with the Microspheres was achieved through the preparation of floating Microspheres by the Modified Emulsion solvent Diffusion method. In the present study attempt has been made to develop sustained released drug delivery system by formulating the floating Microspheres of Sumatriptan using White Rice Flour powder as a natural polymer which is biodegradable, biocompatible, nontoxic, economically cheap cost, devoid of adverse and side effects and easily availability. Sumatriptan Succinate is the succinate salt form of sumatriptan, a member of the triptan class of compounds with anti-migraine property. Sumatriptan succinate selectively binds to and activates serotonin 5-HT1 receptors. The 12 batches of floating Microspheres (MF1 to MF12) were formulated by Modified Emulsion solvent Diffusion method using different ratio of polymers like White Rice Flour power, HPMC K4M and Carbopol. The formulated Microspheres were evaluated by means of different parameters like shape and density of Microsphere, drug content uniformity, In-vitro buoyancy, swelling Index, In-vitro dissolution studies. The formulation MF6 has better sustained release when compared other formulations, hence we conclude that the combination of White Rice Flour powder, HPMC K4M shows better Gastric retention time which sustains the release of the dosage form.

Development of posaconazole nanocrystalline solid dispersion: preparation, characterization and in vivo evaluation

Objective Posaconazole (PCZ) is an antifungal drug, which acts by inhibiting the lanosterol-14α-demethylase enzyme. It is a biopharmaceutical classification system class II drug with its bioavailability being limited by poor aqueous solubility. The aim of this study was to improve the oral bioavailability of PCZ by preparing nanocrystalline solid dispersion (NCS). Methods PCZ-NCS was prepared by a combination of precipitation and high-pressure homogenization followed by freeze-drying. Several different surfactants and polymers were screened to produce NCS with smaller particle size and higher stability. Results The optimized NCS formulation containing 0.2% Eudragit S100 and 0.2% SLS was found to provide the average particle size of 73.31 ± 4.7 nm with a polydispersity index of 0.23 ± 0.03. Scanning electron microscopy revealed the preparation of homogeneous and rounded particles. Differential scanning calorimetry and X-ray diffraction confirmed crystalline nature of NCS. Nanonization increased the saturation solubility of PCZ by about 18-fold in comparison with the neat drug. Intrinsic dissolution study showed 93% dissolution of PCZ within the first 10 min. In vivo pharmacokinetic study in Wistar rats showed that Cmax and AUCtotal of PCZ-NCS increased by 2.58- and 2.64-fold compared to the marketed formulation. Conclusion PCZ-NCS formulation presents a viable approach for enhancing the oral bioavailability of PCZ.

Development and Validation of UV-VIS Spectrophotometric Method for Estimation of Methylprednisolone from Dissolution Media

A simple, accurate UV-Spectrophotometric method has been developed using a dissolution media, 0.1% Tween 20 as a solvent to determine the Methylprednisolone. At a predetermined λmax of 245 nm, method was proved linear in the range of 5- 40 μg/ml with good correlation coefficient (R2= 0.998) and excellent recovery (between 98 and 101%). This method was successfully applied to the determination of methylprednisolone from dissolution media, 0.1% Tween 20 solution. This method can be employed for the dissolution study of methylprednisolone in injectable suspension.

Development And Validation of UV-VIS Spectrophotometric Method for Determination of Triamcinolone from Dissolution Media

A simple, accurate UV-VIS Spectrophotometric method has been developed using a dissolution media, Tween 20 (0.15%) as a solvent to determine the Triamcinolone. At predetermined λmax of 240 nm, method was proved linear in the range of 10-50 µg/ml with good correlation coefficient (R2= 0.998) and excellent recovery (between 98 and 101%). This method was successfully applied to the determination of Triamcinolone from dissolution media, 0.15% Tween 20 aqueous solution. This method can be employed for the dissolution study of Triamcinolone in injectable suspension.

Enhancing the oral bioavailability of fisetin: polysaccharide-based self nano-emulsifying spheroids for colon-targeted delivery.

Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS.

Fabrication of Ciprofloxacin-Loaded Sodium Alginate Nanobeads Coated with Thiol-Anchored Chitosan Using B-390 Encapsulator Following Optimization by DoE.

Most infectious diseases of the gastrointestinal tract can easily be treated by exploiting the already available antibiotics with the change in administration approach and delivery system. Ciprofloxacin (CIP) is used as a drug of choice for many bacterial infections; however, long-term therapy and off-site drug accumulation lead to an increased risk of tendinitis and peripheral neuropathy. To overcome this issue, nanotechnology is being exploited to encapsulate antibiotics within polymeric structures, which not only facilitates dose maintenance at the infection site but also limits off-site side effects. Here, sodium alginate (SA) and thiol-anchored chitosan (TC) were used to encapsulate CIP via a calcium chloride (CaCl2) cross-linker. For this purpose, the B-390 encapsulator was employed in the preparation of nanobeads using a simple technique. The hydrogel-like sample was then freeze-dried, using trehalose or mannitol as a lyoprotectant, to obtain a fine dry powder. Design of Experiment (DoE) was utilized to optimize the nanobead production, in which the influence of different independent variables was studied for their outcome on the polydispersity index (PDI), particle size, zeta potential, and percentage encapsulation efficiency (% EE). In vitro dissolution studies were performed in simulated saliva fluid, simulated gastric fluid, and simulated intestinal fluid. Antibacterial and anti-inflammatory studies were also performed along with cytotoxicity profiling. By and large, the study presented positive outcomes, proving the advantage of using nanotechnology in fabricating new delivery approaches using already available antibiotics.

Nucleotides as new co-formers in co-amorphous systems: Enhanced dissolution rate, water solubility and physical stability

Developing co-amorphous systems is an attractive strategy to improve the dissolution rate of poorly water-soluble drugs. Various co-formers have been investigated. However, previous studies revealed that it is a challenge to develop satisfied acidic co-formers, e.g., acidic amino acids showed much poorer co-former properties than neutral and basic amino acids. Only a few acidic co-formers have been reported, such as aspartic acid, glutamic acid, and some other organic acids. Thus, this study aims to explore the possibility of adenosine monophosphate and adenosine diphosphate used as acidic co-formers. Mebendazole, celecoxib and tadalafil were used as the model drugs. The drug-co-former co-amorphous systems were prepared via ball milling and confirmed using XRPD. The dissolution study suggested that the solubility and dissolution rate of the drug-co-formers systems were increased significantly compared to the corresponding crystalline and amorphous drugs. The stability study revealed that using the two nucleotides as co-formers enhanced the physical stability of pure amorphous drugs. Molecular interactions were observed in MEB-co-former and TAD-co-former systems and positively affected the pharmaceutical performance of the investigated co-amorphous systems. In conclusion, the two nucleotides could be promising potential acidic co-formers for co-amorphous systems.

Moxifloxacin-loaded nanoparticles of thiolated xyloglucan for ocular drug delivery: Permeation, mucoadhesion and pharmacokinetic evaluation

The current study goal was to improve mucoadhesive potential and ocular pharmacokinetics of nanoparticles of thiolated xyloglucan (TXGN) containing moxifloxacin (MXF). Thiolation of xyloglucan (XGN) was achieved with esterification with 3-mercaptopropionic acid. TXGN was characterized by NMR and FTIR analysis. The nanoparticles of TXGN were prepared using ionic-gelation method and evaluate the antibacterial properties. TXGN and nanoparticles were determined to possess 0.06 and 0.08 mmol of thiol groups/mg of polymer by Ellman's method. The ex-vivo bioadhesion time of TXGN and nanoparticles was higher than XGN in a comparative assessment of their mucoadhesive properties. The creation of a disulfide link between mucus and TXGN is responsible for the enhanced mucoadhesive properties of TXGN (1-fold) and nanoparticles (2-fold) over XGN. Improved MXF penetration in nanoparticulate formulation (80 %) based on TXGN was demonstrated in an ex-vivo permeation research utilizing rabbit cornea. Dissolution study showed 95 % release of MXF from nanoparticles. SEM images of nanoparticles showed spherical shape and cell viability assay showed nontoxic behavior when tested on RPE cell line. Antibacterial analysis revealed a zone of inhibition of 31.5 ± 0.5 mm for MXF, while NXM3 exhibited an expanded zone of 35.5 ± 0.4 mm (p < 0.001). In conclusion, thiolation of XGN improves its bioadhesion, permeation, ocular-retention and pharmacokinetics of MXF.

Development of Physiologically Based Biopharmaceutical Model (PBBM) for Felodipine Prolonged-Release Tablet as useful tool for prediction of formulation.

Physiologically Based Biopharmaceutical Models (PBBMs) are advanced tools that integrate physiological parameters with drug-specific properties to simulate drug behavior in vivo. In this study, we present the development of a PBBM specifically tailored for felodipine prolonged-release (PR) tablet formulations. Felodipine, a potent calcium channel blocker, is widely used for the treatment of hypertension and angina pectoris. Prolonged-release formulations aim to provide controlled drug release, ensuring sustained therapeutic effect with reduced dosing frequency and minimized adverse effects. Our PBBM incorporates key physiological processes such as gastrointestinal transit, drug dissolution, absorption, distribution, metabolism, and elimination. Data from in vitro dissolution studies, preclinical pharmacokinetics, and clinical observations are integrated to parameterize the model accurately. Special attention is given to the physicochemical properties of felodipine and the release characteristics of the PR tablet formulation. Validation of the PBBM is conducted against clinical pharmacokinetic data obtained from bioequivalence studies and population pharmacokinetic analyses of felodipine PR tablets. The model may demonstrate excellent predictive performance, accurately capturing plasma concentration-time profiles across different dosing regimens and patient populations. The developed PBBM provides valuable insights into the biopharmaceutical behavior of felodipine PR tablets, facilitating rational formulation design, dosage regimen optimization, and therapeutic individualization. It serves as a powerful tool for drug developers, regulatory agencies, and clinicians to enhance the efficiency and effectiveness of drug development and clinical pharmacotherapy