Formulation and Evaluation of Nasal Microspheres

Montelukast was first approved for clinical use by the US FDA in 1998 as Merck's brand name Singulair. Montelukast is a member of quinolines, a monocarboxylic acid and an aliphatic sulfide (Figure 1). It has a role as a leukotriene antagonist, an anti-asthmatic drug and an anti-arrhythmia drug. It is a conjugate acid of a montelukast (1-). The medication is a member of the leukotriene receptor antagonist (LTRA) category of drugs (1). Although capable of demonstrating effectiveness, the use of such LTRAs like montelukast is typically in addition to or complementary with the use of inhaled corticosteroids or other agents in asthma step therapy. Regardless, in 2008-2009, there were FDA-led investigations into the possibility of montelukast to elicit neuropsychiatric effects like agitation, hallucinations, suicidal behaviour, and others in individuals who used the medication (2) And although these kinds of effects are currently included in the official prescribing information for montelukast, the drug still sees extensive use worldwide via millions of prescriptions annually and has since become available as a generic and as a brand name product (3).

Figure 1: Chemical Structure of Montelukast

The study aims to develop and evaluate nasal microspheres containing Montelukast for targeted drug delivery, improving bioavailability, patient compliance, reducing dosing frequency, minimizing side effects, and optimizing size and shape. It also evaluates drug release profiles, develops a stable manufacturing process, and compares with existing systems.

MATERIALS AND METHODS

2.1. Preformulation Studies

The drug samples were examined for appearance, color, and odor. The melting point of drug was determined using the capillary method, where a fine powder of the drug was filled in a glass capillary tube and dipped in liquid paraffin. Solubility was also determined in various buffers of different pH values, with the drug being dissolved in different beakers containing solvents and shaken for 24 hours at regular intervals (6-10).

2.2. Preparation of Chitosan Nasal Microspheres

Chitosan microspheres were prepared using a simple w/o emulsification-cross linking process using liquid paraffin as an external phase. Chitosan was dissolved in a 2% aqueous acetic acid solution, then added to 100 mL of liquid paraffin containing 0.2% w/v of DOSS as a stabilizer. Montelukast was added to the chitosan solution, and the dispersion was added to the paraffin. A 25% solution of glutaraldehyde was added to the emulsion, and stirring was continued for 2 hours. The hardened microspheres were separated by vacuum filtration, washed with hexane to remove oil, and washed with distilled water to remove unreacted GA. The microspheres were air dried for 24 hours and stored in a vacuum desiccator until further use (11-13).

2.3. Characterization of Chitosan Nasal Microspheres

The prepared Chitosan Nasal Microspheres were evaluated for physical appearance, particle size, Entrapment Efficiency, swelling index, drug release and stability (14-16).

RESULTS AND DISCUSSION

3.1. Preformulation Studies

3.1.1. Organoleptic Characteristics

The drug sample was analyzed for physical appearance and compared with the standard (Table 1).

Table 1: Observed organoleptic properties of drug sample

3.1.2. Melting Point Determination

The Indian pharmacopeia recommended the capillary method for melting point determination, and the standard melting point of drug was found to be 127.36 ± 0.384°C, within the reported range of 115–149°C, indicating the drug sample's purity.

3.1.3. Solubility

Solubility check is also a key parameter in drug development as it determines the ability of a drug to dissolve in various solvents. This information is crucial for designing dosage forms that ensure optimal absorption and bioavailability of the drug (Table 2).

Table 2: Solubility Study of Montelukast

3.1.4. Loss on Drying

The percentage loss on drying was found to be 0.16 %.

3.1.5. Partition Coefficient

The study showed that major portion of drug was partitioned towards organic phase. Partition Coefficient of montelukast was found to be 2.69. It indicated that drug is lipophilic in nature.

3.2.  Evaluation Parameter of Optimized Formulation of Montelukast loaded Nasal Microspheres

The study focuses on the spherical particle size of chitosan microspheres, which are essential for the formation of niosomal vesicles. The hydrophilic hydrophobic segments of non-ionic surfactants play a crucial role in the formation of these vesicles, and the size distribution of microspheres is considered suitable for nasal administration. The study focuses on the spherical particle size of chitosan microspheres, which are essential for the formation of niosomal vesicles. The determination of drug content shows good uniformity, with drug contents close to theoretical values and good encapsulation efficiency between 88% and 96%. Encapsulation efficiencies are always high, increasing with increasing drug to polymer weight ratios. Swelling studies were conducted to determine the swelling ability of spray dried microspheres, with the maximum swelling observed with microspheres containing the highest concentration of polymer. This study was important for studying clearance of drug from the nasal cavity, as it suggests that administration of microspheres lowers clearance due to the process of taking up water and swelling, leading to reduced mucocilliary clearance. Mucoadhesion studies were carried out to ensure the adhesion of the formulation to the mucosa for a prolonged period of time at the site of absorption. Percent mucoadhesion increased with increase in polymer concentration. Strong adhesive bonds are essential for the establishment of strong intimate molecular contact between the polymer and glycoprotein chain (Table 3).

Table 3: Characterization of Chitosan Based Microspheres