Formulation and Evaluation of Beta- Blocker drug loaded Invasome for the treatment of Hypertension

Administration of drugs into the body via application of the formulation onto the skin is a non-invasive technique that helps in treatment of different diseases. Transdermal administration of drugs is better than the oral route of administration in many aspects. The technique has large areas available for sustained release of drugs and absorption of drugs. Transdermal administration of drugs enhances compliance among patients and ensures a reliable pharmacokinetics profile. The method minimizes the risks of side effects, maximizes the bioavailability of drugs, and eliminates first-pass effect. Different methods can be used to deliver drugs transdermally, including the use of patches and gel.[1][2]

Moreover, transdermal delivery is a better choice for people who are more sensitive to the side effects associated with their digestion system, as it can minimize the adverse reactions to the oral drugs. But The drug is unable to penetrate through the protective layer of skin called stratum corneum. It needs modification to ensure ease of drug delivery for drugs with poor penetration. [3]

In case of Nebivolol hydrochloride, which acts as a selective β1-adreno receptor blocker, is known for its unique hemodynamic properties, including reduction in peripheral vascular resistance and no effect on cardiac output. Although the oral bioavailability of nebivolol hydrochloride varies between 12% and 96%, making it highly metabolized, it remains an excellent candidate for transdermal administration owing to its unique attributes such as low molecular weight, short biological half-life, medium lipophilicity, and low dose requirements. [4]

Nebivolol hydrochloride specifically blocks β1 receptors to neutralize the actions of epinephrine, resulting in reduced heart rate and blood pressure. Additionally, β adrenergic inhibitors prevent the production of renin that constricts blood vessels. Increased doses of nebivolol hydrochloride can also block β2 receptors[4]

Invasomes are a newly introduced delivery system of drugs into the skin using vesicular drug delivery systems. The phospholipids affect the skin's lipophilic layer by increasing its permeability, thus allowing better penetration of the drugs through the skin layer. The invasomes are soft vesicles made up of phospholipids, terpenes, and ethanol.[5] Phospholipid affects the stratum corneum bilayer by increasing fluidity, hydration of skin, and interaction of ceramides present in the skin barrier leading to the formation of pores.[6] The effect of ethanol on skin permeation is that it acts as a permeation enhancer by increasing the softness of the skin barrier compared to liposomes, making the bi-lipid layer more flexible. [7] Ethanol also makes vesicles more flexible, allowing their passage through damaged SC. Terpenes act as penetration enhancers by disrupting the existing hydrogen bond in the SC between ceramides and forming new ones with hydrogen donors or acceptors.[8]

MATERIAL AND METHOD

Materials:

Nebivolol Hydrochloride and soy lecthin was purchased from Dhamtec pharma & Consutant, Mumbai, Ethanol and Eugenol procure from Naveen Chemicals, India, Distilled water was prepared in the college laboratory.

Method:

Methodology:

FTIR: The invasomal dosage form is often tested for the compatibility of the drug and excipients using FTIR spectroscopy, which indicates the presence of unique peaks of terpenes, ethanol, and phospholipids. The formulation's stability is assured by the absence of any shift in the peaks, indicating no chemical reaction. [9]

Material Composition of Nebivolol Hcl Loaded Invasome:

Preparation of Nebivolol Hcl Loaded Invasome:

The drugs, phospholipids, ethanol, and terpenes such as eugenol are all dissolved in one organic solvent through the ethanol injection method, after which the mixture is injected into distilled water with constant stirring. The diffusion of ethanol leads to the formation of liposomes due to the rapid merging of two miscible solvents. The use of the above method results in the formation of small, homogeneous invasomes.[9]

Characterization of invasome:

Physical evaluation of invasome:

The polydispersity index (PDI) and the particle size of the invasomes were determined using the dynamic light scattering machine (Malvern Zetasizer). This technique allows for detailed determination of the particle size profile, thus ensuring that the exact PDI of the invasomes is determined. The two parameters are crucial in determining the formulations' stability and uniformity. [10]

Entrapment efficiency:

Entrapment efficiency of invasomal formulation was measured by employing ultracentrifugation method. Invsomal formulation was centrifuged by using a chilled centrifugation machine keeping the temperature constant at 4 degrees Celsius. Further, dilution of collected sedments was carried out using ethanol. UV Spectroscopy was employed for measurement at wavelength 282nm. It can be calculated using formula: [5]

EE=total drug -free drug /total drug *100

Morphological Evaluation:

The shape and surface characteristicsof the Invasome was observed by scanning electron microscopy.[11]

In- Vitro Drug study:

The in vitro drug release study for this research was performed through the use of the Franz diffusion cell. The effective area for penetration was recorded to be 0.184 cm², whereas the volume of the receptor cell was found to be 13 mL. The donor cell containing the optimized invasomal dosage form was positioned above the receptor cell that had a pH of 7.4. The experiment was conducted for 12 hours at a temperature of 37±1?C and under continuous stirring of 600 rpm. Samples were taken from the receptor cell after certain time points, including 1, 2, 3, 4, 5, 6, 8, and 12 hours, and analyzed for nebivolol hydrochlorides concentration via UV spectrophotometry at 282 nm.

RESULT AND DISCUSSION:

FTIR:

Fig. FTIR of Nebivolol Hydrochloride

PDI:

SEM:

EE%

In- Vitro Drug Release: