Formulation and Evaluation of Fast Dissolving Film of Lisinopril

1.2 Oral Dissolving Film Theory:

In this setup, a thin film is present. Sublingual administration improves bioavailability because the drug dissolves faster and bypasses first-pass metabolism. Because SA is more easily absorbed, it breaks down and dissolves rapidly in the mouth. The following are the three main types of oral films:

1. Films have a rapid dissolving or releasing time (when held to the mouth).

2. Mucoadhesive films that dissolve (for use in the buccal or gingival area). The third option is buccal mucosa-adhering sustained-release films. [3]

1.3 Mechanism of oral mouth dissolving film theory:

Figure 1: Mechanism of oral mouth dissolving film theory

Figure 2: Mouth-dissolving film

1.4 Need for fast-dissolving drug delivery systems: [4]

Patients with dysphasia may find it easier to take their medication as prescribed when it dissolves quickly. If a medicine is subject to patent protection, the marketing department will find that FDDS is a useful tool for managing the medical life cycle.

METHODS

1 Solvent casting method [81]

Fast dissolving films were prepared by solvent casting method as per the composition shown in table 1.In this method, the required quantity of water soluble polymer Sodium carboxymethyl cellulose was dissolved in distilled water in a beaker (covered with aluminium foil) with continuous stirring on magnetic stirrer to make required percentage of polymer solution and then the weighed quantity of ingredients like lisinopril as drug , glycerol as plasticizer, and menthol a flavor, Saccharin sodium as Sweetening agent was dissolved in distilled water in another beaker and then this mixture was added to the polymer solution. After continuous stirring for 2 hours the solution was left undisturbed for 12 – 16 hours to remove all the air bubbles. This polymeric – drug solution was then poured on to the moulds, allowed to air dry , packed in aluminum foil and then stored in desiccators until use.

Advantages

• Film has a fine gloss and is devoid of flaws like die lines, and it has superior uniformity of thickness and clarity to extrusion.

•  The recommended finished film thickness is typically 12-100 m; however different

thicknesses are available to fulfill API loading and dissolving needs. The film has better physical qualitiesand is more flexible.

Disadvantages:

1.   The polymer needs to be soluble in water or a volatile solvent.

2.    It is ideal to generate a stable solution with a reasonable minimum solid content and viscosity.

3.    It must be feasible to create a homogeneous film and be released from the casting support.

6.2.2 Experimental Design [82]

Box–Behnken design was employed to studythe effect of each independent variable on dependent variables Disintegration time (sec), Drug content (%) and Drug release (%) Lisinopril film formulation were prepared by solvent casting method.The Lisinopril film were optimized by using Box-Behnken Experimental Design (3 Factor, 2 Level, and DesignExpert Version 13). The independent variables selected were Sodium carboxymethyl cellulose(mg) (X1), Sodium starch glycolate(mg) (X2) and Glycerol(ml) (X3) with their low and high levels for preparing 13 run of formulations and dependent variable selected were Disintegration time(sec) ,( wetting time (sec)and Drug release (%). Finally optimized was selected for further characterization.

Table 14: DOE suggested and experimental batches

Calculation for Petri Dish

Diameter of Petri dish = 9cm Area of circle =

= 3.14 × 4.5 × 4.5

=63.585 cm2

Area of Single patch = L × W Area of Single patch =2×2

= 4 cm2

So, Total no of films = 63.585 / 4

=15.89

Total amount of drug requires = i.e. (Total no of films × Dose of drug) = 15.896×10 Total amount of drug require =158.96 mg

Table 15: List of independent variable and dependent variable on box Behnken design

RESULT AND DISCUSSION  

7.1 PREFORMULATION STUDY

7.1.1 Identification of drug

1.1.1.1 Appearance

7.1.1.2 Active pharmaceutical ingredient: Lisinopril

7.1.2 Melting point

The capillary tube method was used to determine the melting point. The melting point of Lisinopril was found to be 164 and recorded melting point of Lisinopril 162-165 °C.

Table 16: Observation of melting point

Figure 10: Melting point of Lisinopril

7.1.3 Solubility study of lisinopril

The solubility study of lisinopril across various mediums reveals that methanol provides the highest solubility at 48.16 mg/mL, making it the most effective solvent for dissolving lisinopril. Ethanol (30.14 mg/mL) and distilled water (29.14 mg/mL) also demonstrate good solubility, suggesting they are suitable alternatives for formulation purposes. 

Table 17: Solubility in different Medium

Figure 11: Solubility in different Medium

7.1.2 Spectrophotometric characterization of Lisinopril in UV Spectroscopy

7.1.2.1 Detection of Absorption Maxima (λ max)

Table 18: Observation of λmax

7.1.2.2 Calibration curve

Table 19: Calibration curve in Distilled water

Figure 12: Calibration curve in Distilled water

7.1.2.2.2 Calibration curve in Methanol

Table 20: Calibration curve in Methanol

Figure 13: Calibration curve in Methanol

 7.1.2.2.3 Calibration curve in Ethanol

Table 21: Calibration curve in Ethanol

Figure 14: Calibration curve in ethanol

7.1.2.2.4 Calibration curve in Phosphate buffer pH 6.8

Table 22: Calibration curve in Phosphate buffer pH 6.8

Figure 15: Calibration curve in Phosphate buffer pH 6.8

7.1.2.2.5 Calibration curve in Phosphate buffer pH 7.4

Table 23: Calibration curve in Phosphate buffer pH 7.4

Figure 16: Calibration curve in Phosphate buffer pH 7.4

7.1.2.2.6 Calibration curve in Acidic buffer pH 1.2

Figure 17: Calibration curve in Acidic buffer pH 1.2

7.2 Post Formulation Study

7.2.1 Transparency

Physical appearance of the formulations. The clear transparency indicates that there are no visible particles or impurities present in any of the formulations. Additionally, the optimization of batch L8 suggests that it meets the desired criteria for clarity and uniformity, making it the preferred choice for further development or use in applications requiring clear formulations.

Table 25: Transparency of L1to L13

7.2.2Weight Variation

The optimized batch (L8) of the fast dissolving film formulation exhibited a weight variation of 46.4 ± 0.24. This result indicates a consistent weight among different units of the film, ensuring uniformity in dosage. A low variation in weight is crucial for maintaining the quality and efficacy of the pharmaceutical product. Therefore, batch L8 meets the desired standards for weight uniformity in the formulation.

26: Weight Variation L1to L13

Moisture content data, formulation L8 emerges as the optimized choice due to its comparatively low moisture content of 2.7% ± 0.546.

27: Moisture content L1to L13

7.2.4 Thickness (mm)

The optimized batch (L8) of the fast dissolving film formulation exhibited a thickness of 0.14 ± 0.010 mm.

28: Thickness (mm) L1to L13

7.2.5 Folding endurance study

The optimized batch (l8) of the fast dissolving film formulation demonstrated excellent folding endurance, with a value exceeding 300.

29: Folding endurance L1to L13

7.2.6 Surface pH

The optimized fast dissolving film formulation (l8) exhibited a pH of 6.1.

Table 30: PH of L1to L13

7.2.7 Drug Content (%)

Formulation L8 exhibits the highest drug content among the tested formulations, with a percentage of 96.48%.

Table 31: Drug Content (%) of L1to L13

ANOVA for Linear model Response 2: Drug content

Factor coding is coded.

Sum of squares is Type III - Partial

Figure 18: Counter plot

Figure 20: 3D Surface plot

7.2.8 Tensile strength (N/mm²)

The tensile strength of formulation L8 is determined to be 3.4 ± 0.14 N/mm², positioning it as the optimized batch among the formulations tested. This suggests that formulation L8 possesses favorable mechanical characteristics, which are crucial for the integrity and performance of the product.

Table 32: Tensile strength (N/mm²) of L1to L13

7.2.9 Percentage elongation (%)

Percentage elongation for various formulations ranges from 13.6% to 45.26%.      

Table 33: Percentage elongation (%) of L1to L13

7.2.10. in Vitro Disintegration Time

The disintegration time for various formulations of fast-dissolving oral films (batch L8) ranges from 22 to 62 seconds.

Table 34: Disintegration Time of L1to L13

ANOVA for Linear model Response 1: disintegration time

Factor coding is coded.

Sum of squares is Type III - Partial

Figure 21: Counter plot