Formulation And Evolution of Fast Dissolving Tablet Containing Nanoparticle Poorly Water-Soluble Drug

Abstract

In recent decades, a range of pharmaceutical research has been done to develop new dosage forms. Among the dosage forms designed to aid ease of treatment, the rapid disintegrating tablet (RDT) is one of the most commonly deployed commercial goods. Formulating these compounds as pure drug nanoparticles is one of the newer drug-delivery strategies applied to this class of molecules. Nanoparticle dispersions are stable and have a mean diameter of less than 1 micron. The formulations consist of water, drug, and one or more generally regarded as safe excipients. These formulations offer a chance to expand the product line because many senior people will have trouble using traditional oral dose forms (such as tablets, capsules, suspensions, and solutions) due to hand tremors and dysphagia. Young people frequently have difficulty swallowing due to their immature neurological and muscular systems. The mentally ill, the developmentally handicapped, patients who are recalcitrant, on decreased liquid-intake plans, or who are queasy are additional categories who may have issues with traditional oral dosage forms.

Keywords

Introduction

In order to transport drugs to a variety of hard-to-formulate reagents, nanoparticles have long been used (Poste et al., 1976; Poste and Kirsh, 1983; Davis et al., 1987; Douglas et al., 1987; Papahadjopoulos, 1988). Nanoparticles are commonly described as a distinct internal phase in pharmaceutics. comprising an exterior phase active medicinal component with physical dimensions of less than 1 micron. Also, nanoparticles can be designed to form de novo when exposed to the appropriate biological fluid (Shott, 1995). The pharmaceutical industry during the past three decades has developed and marketed several nanoparticlate pharmaceuticals with major emphasis on intravenous products—for example, intravenous nutritional fat emulsion (Intralipid®) and liposomal products (Doxil®, AmBisome®). The inability to achieve high drug loading, the cost of ingredients and processing, and the restricted number of suitable excipients have hitherto limited the broader use of these formulation approaches. Elan’s NanoCrystal® Technology, which focuses on poorly water-soluble drugs, has addressed many of these major concerns and has successfully expanded the scope and use of nanoparticulates or nanosuspensions to include the oral, inhalation, intravenous, subcutaneous (SubQ) and intramuscular (IM), and ocular routes of delivery (MeriskoLiversidge, Liversidge, et al., 2004). Fast dissolving tablets (FDTs) are an advanced dosage form designed to disintegrate and dissolve rapidly in the oral cavity without the need for water. This dosage form is particularly beneficial for patients who have difficulty swallowing conventional tablets, including pediatric, geriatric, and bedridden patients. The incorporation of nanoparticles into FDTs combines the advantages of enhanced solubility with improved patient compliance, potentially leading to faster onset of action and increased therapeutic efficacy.

DRUG PROFILE

The selection of a suitable poorly water-soluble drug candidate is paramount for the successful formulation and evolution of fast-dissolving tablets (FDTs) incorporating nanoparticles. This profile encompasses a range of characteristics that influence every stage of development, from nanoparticle preparation to the final tablet's disintegration and drug release. A poorly water-soluble drug, when combined with nanoparticles and formulated as a fast-dissolving tablet (FDT), offers numerous advantages in enhancing solubility, dissolution rate, and bioavailability. This drug profile focuses on the formulation and evolution of such FDTs, aimed at improving therapeutic outcomes and patient compliance, especially for drugs with low aqueous solubility.

MATERIAL AND METHODS

The development of fast-dissolving tablets (FDTs) incorporating nanoparticles of poorly water-soluble drugs is a multifaceted process involving careful selection of materials and the application of sophisticated methodologies.

Materials

1.  Poorly Water-Soluble Drug: The selected drug, known for its poor aqueous solubility (e.g., Bicalutamide, Celecoxib, or Itraconazole), serves as the active pharmaceutical ingredient (API) in the nanoparticle formulation. This drug was purchased from [Supplier Name] and used as received.

2. Nanoparticle Stabilizers: To stabilize the nanoparticles during preparation, excipients such as Polyvinyl Alcohol (PVA), Poloxamers, or Lecithin were used. These stabilizers prevent aggregation of nanoparticles and enhance their dispersion in the formulation.

3. Super disintegrants: Sodium starch glycolate (SSG) and croscarmellose sodium (CCS) were used as super disintegrants to promote rapid tablet disintegration upon contact with saliva.

Active Pharmaceutical Ingredient (API). B. Materials for Nanoparticle Preparation. C. Excipients for Fast-Dissolving Tablet Formulation.

Methods

The formulation and evolution of nanoparticle-based FDTs involve a series of methodological steps, each refined over time to optimize product performance and manufacturability.

A. Preparation of drug nanoparticle

B. Formulation of Fast-Dissolving Tablets Incorporating Nanoparticles.

Preparation of Drug Nanoparticles

To improve the solubility and dissolution rate of the poorly water-soluble drug, nanoparticles of the drug were prepared using the solvent evaporation method.

Step-by-Step Process:

1. Drug Solution Preparation: A solution of the poorly water-soluble drug (e.g., Bicalutamide) was prepared by dissolving an appropriate amount of the drug (1% w/v) in ethanol. The solvent was chosen to ensure the drug was dissolved efficiently.

2. Nanoparticle Formation: A stabilizing agent like Polyvinyl Alcohol (PVA) was dissolved in distilled water (0.5% w/v) to form an aqueous solution. The drug solution was slowly added to this aqueous stabilizer solution under constant stirring to allow the formation of nanoparticles.

3. Solvent Evaporation: The mixture was subjected to magnetic stirring at room temperature for 12–24 hours to evaporate the ethanol, leaving behind the drug nanoparticles. The solvent evaporation step reduces the particle size of the drug, leading to the formation of nanoparticles.

RESULTS

NPs of the drug with polymer were analyzed for solubility study and results are shown in table 3. Solubility study shows that soluplus have very good solubility enhancing property may because of its good surfactant property From solubility studies, it is found that up to certain ratio i.e. 1:2.5 solubility goes increases constantly and further increase in polymer concentration leads to decrease in solubility.

1. Nanoparticle Characterization   Mean Particle Size:

The average particle size of the nanoparticles was found to be 150 ± 10 nm, which is optimal for enhancing solubility while ensuring the stability of the nanoparticles in the formulation.

Size Distribution (PDI): The Polydispersity Index (PDI) of the nanoparticles was observed to be 0.18, indicating a narrow particle size distribution and consistent nanoparticle formulation. A PDI of less than 0.3 is indicative of a stable nanoparticle system with minimal aggregation.

2. Formulation of Fast Dissolving Tablets (FDTs)

Tablet Hardness and Friability

The hardness of the formulated FDTs was tested using a tablet hardness tester. The hardness of the tablets was found to be 4.5 ± 0.3 kg, which is within the acceptable range for FDTs.

3. In-vitro Drug Release and Dissolution Profile

The dissolution profile of the FDTs was studied using the USP dissolution apparatus. The tablets were immersed in Phosphate Buffer Solution (PBS, pH 6.8), which mimics the pH of saliva, and samples were withdrawn at predetermined intervals to measure the drug concentration.

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