Development and evaluation of a palatable multiparticulate orodispersible tablet formulation of a poorly water-soluble antihypertensive using nanostructured lipid carriers for enhanced bioavailability.

Project Abstract

The current study focuses on the development and evaluation of a palatable multiparticulate orodispersible tablet (ODT) formulation of a poorly water-soluble antihypertensive drug, leveraging nanostructured lipid carriers (NLCs) to enhance oral bioavailability and patient compliance. The research employed a bi-phasic approach first, the design and optimization of NLCs to solubilize the hydrophobic antihypertensive molecule, and second, the formulation of a robust ODT containing optimized nanoparticles within a suitable multiparticulate matrix. NLCs were prepared via a high-shear homogenization and ultrasonication method using a blend of solid and liquid lipids with surfactants to achieve a particle size in the sub-200 nm range, low polydispersity, and high drug loading efficiency. Comprehensive characterization included particle size distribution, zeta potential, entrapment efficiency, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and transmission electron microscopy to confirm morphology and stability. In vitro release studies demonstrated a biphasic profile with an initial rapid release to facilitate quick onset of action, followed by sustained release over 8–12 hours, attributed to lipid matrix diffusion and erosion. The NLCs were then incorporated into a multiparticulate ODT using superdisintegrants, taste-masking agents, and flavoring excipients to achieve rapid disintegration (<30 seconds) in the oral cavity and pleasant mouthfeel while maintaining drug stability. To ensure patient acceptability, a palatability assessment was conducted using an ex vivo taste pad model and a small-scale human panel, revealing high acceptance for flavor and minimized aftertaste. Pharmacokinetic studies in a suitable animal model indicated enhanced Cmax and AUC for the NLC-ODT compared with a conventional coarse drug powder and marketed formulations, suggesting improved oral bioavailability likely due to increased solubility, reduced first-pass metabolism, and favorable mucosal absorption. Stability studies under accelerated and long-term conditions demonstrated maintained physicochemical integrity, drug content, and release characteristics for up to six months in appropriate packaging. A simulated in vivo-in vitro correlation (IVIVC) was established by correlating dissolution profiles with pharmacokinetic parameters, supporting predictive performance of the ODT under real-world conditions. The formulation exhibited robust mechanical properties suitable for packaging and handling, with disintegration time not exceeding 60 seconds and friability within pharmacopeial limits. Risk assessment identified critical quality attributes such as drug loading efficiency, nanoparticle stability, and taste masking as pivotal drivers of product performance, prompting optimization of lipid ratios and surfactant selection. Overall, the palatable multiparticulate ODT leveraging NLCs demonstrated superior solubility enhancement, improved bioavailability, rapid onset, and patient-centric characteristics, presenting a viable strategy for delivering poorly water-soluble antihypertensives. The study provides a framework for translating nanostructured lipid carrier-based ODTs into clinically relevant dosage forms, with implications for improved adherence and therapeutic outcomes in hypertension management. Future work will focus on clinical validation, long-term safety assessment, and scalability for industrial manufacturing.

Project Overview

What This Project Is About

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This project looks at making a small, easy-to-swallow medicine piece (a tablet) that dissolves quickly in the mouth. The drug is an antihypertensive, meaning it helps lower blood pressure, but it doesn’t dissolve well in water. The plan is to use tiny carriers called nanostructured lipid carriers to improve how well the drug is absorbed in the body, so you get the same effect with a lower dose.

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The Problem It Addresses

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Many effective blood pressure drugs don’t dissolve well in water, which can limit how much the body can absorb and use. This leads to variable effects and more frequent dosing. The project aims to overcome this by packaging the drug in a delivery system that enhances solubility and absorption, while keeping the tablet palatable and easy to take.

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Objectives of the Project

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1. Explain what nanostructured lipid carriers are and why they help with drug delivery.
2. Formulate a palatable multiparticulate orodispersible tablet containing the antihypertensive drug.
3. Assess how well the drug dissolves from the tablet in simulated gastric conditions.
4. Evaluate the taste, mouthfeel, and consumer acceptability of the dosage form.
5. Study the stability of the formulation under different storage conditions.

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What You Will Do Step by Step

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1. Review literature on poorly soluble drugs and orodispersible tablets.
2. Choose appropriate lipid carriers and surfactants for formulation.
3. Prepare and optimize the nanoparticle-based tablet using simple, scalable methods.
4. Test dissolution, solubility, and in vitro release profiles.
5. Evaluate taste masking and mouthfeel with basic sensory tests or expert panels.
6. Perform stability testing and simple analytical checks for API content.
7. Analyze data to see if bioavailability could be improved and justify the findings.

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Expected Outcome

The project should deliver a ready-to-study prototype of a palatable orodispersible tablet with improved drug release and potential bioavailability. It should show that the nanostructured lipid carrier approach can make the drug dissolve faster, maintain taste acceptability, and remain stable enough for practical use.