INTRODUCTION:

Recently, the most common form of delivery of drugs is the oral route. However this system has its oven notable advantage of easy administration, it also has significant drawbacks; namely poor bioavailability due to first pass effect and the tendency to produce rapid both high and low blood level, leading to a need for high and/or frequent dosing, which can be both cost prohibitive and inconvenient¹.

Transdermal delivery of drugs through the skin to the systemic circulation provides a convenient route of administration for a variety of clinical indications.

Pharmaceutical scientists have accepted the challenge of transdermal drug delivery over the last 25 years. Most recently, there is an increasing recognition that the skin can also serve as the port of administration for systemically active drugs. In this case, the drug applied topically will be absorbed first into blood circulation and then be transported to target tissues. This could be rather remote from the site of drug application, to achieve its therapeutic purpose².

Ethosomes are the bilayer lipid vesicles which allow the transfer of drug into deep skin layers and systemic circulation^3,4. Ethosomes are soft, malleable vesicles tailored for enhanced delivery of active agents³. Ethosomes composed of mainly of phospholipids, ethanol (relatively high concentration) and water. These “soft vesicles” represents novel vesicular carrier for enhanced delivery to/through skin⁵.

Nifedipine as a dihydropyridine calcium channel blocker used for the treatment of essential hypertension and angina pectoris as the symptoms of hypertension are experienced in the early morning hours. It is a BCS Class II drug with poor solubility. The plasma half life of Nifedipine is 2 hrs. Hence, it is an ideal candidate for the preparation of ethosomal gel for transdermal drug delivery formulation^6,7.

MATERIALS AND METHODS:

Nifedipine Procured From Mylan pharmaceuticals Ltd, Hyderabad., Provided by Sura Labs, Dilsukhnagar, Hyderabad. Soya lecithin procured from Procured from Research lab Fine chem. Industries (Mumbai). Cholesterol and Methylparaben Procured from Purchased from Merck Limited, Mumbai (India). Ethanol, Triethanolamine and Carbopol 940 procured from Purchased from SD Fine- Chem Limited, Mumbai. Propylene glycol procured from Purchased from Loba Chemie Pvt Ltd. (Mumbai, India).

Preparation of Ethosomal gel:

Preparation of Nifedipine loaded Ethosomes⁹

Nifedipine loaded Ethosomes were prepared by hot method. In this specified amount of Soya lecithin, Cholesterol was dissolved in Ethanol and kept under magnetic stirrer for 30 min. The lipid mixture was heated at 40^OC on magnetic stirrer latter specified amount of Nifedipine was added to ethanol to this propylene glycol was added and it was kept under magnetic stirrer latter lipid solution was added drop by drop and it was kept under magnetic stirrer for 1hr. The solution was kept at 40^oC for 1hr later it was kept for sonication using ultra sonicator for 15 min to reduce the particle size.

Table 1: Composition of Nifedipine Ethosomes formulations (NE1 to NE9)

Excipients	NE1	NE2	NE3	NE4	NE5	NE6	NE7	NE8	NE9
Nifedipine (mg)	10	10	10	10	10	10	10	10	10
Lecithin (Soya lecithin) (mg)	25	25	25	50	50	50	100	100	100
Cholesterol(mg)	5	5	5	5	5	5	5	5	5
Ethanol(ml)	10	15	20	10	15	20	10	15	20
Propylene glycol(mL)	5	5	5	5	5	5	5	5	5
Distilled water (ml)	Up to 20 mL	Up to 20 mL	Up to 20 mL	Up to 20 mL	Up to 20 Ml	Up to 20 mL	Up to 20 mL	Up to 20mL	Up to 20 mL

Table 2: Preparation of Ethosomal gel

Ingredient	Ethosomal gel (%) G1	Ethosomal gel (%) G2
Ethosome	1	1
Carbopol 940	1	2
Propylene glycol	15	15
Propylparaben	0.001	0.001
Methylparaben	0.05	0.05
Triethanolamine	Q.s	Q.s
Water	Q.s	Q.s

The standard calibration plot procedure⁸, Ethosomes evaluations (Percentage yield, Drug Content⁹, Entrapment Efficiency, In vitro dissolution⁹, Release kinetics of optimised formulation, studies, The Ethosomal gel evaluations (Viscosity, Clarity, Homogeneity, Drug Content¹⁰), FTIR^11,12, SEM, procedures adopted from previous papers.

RESULTS AND DISCUSSION:

Calibration Plot of Nifedipine in Phosphate Buffer of pH -5.5:

Standard graph of Nifedipine was plotted as per the procedure in experimental method and its linearity is shown in Table and Fig. The standard graph of Nifedipine showed good linearity with R² of 0.999, which indicates that it obeys “Beer- Lamberts” law.

Fig 1: Calibration curve

Characterization of Ethosomes:

Table 3: Percentage yield, Drug Content, Entrapment Efficiency of all Ethosomes formulations

Formulation	Percentage yield (%)	Drug Content (%)	Entrapment Efficiency (%)
NE1	70.90	69.43	52.39
NE2	65.36	62.19	59.05
NE3	78.19	73.76	67.16
NE4	76.25	77.45	79.22
NE5	92.47	92.31	92.79
NE6	98.53	98.14	97.63
NE7	81.93	78.01	75.48
NE8	93.47	89.35	88.59
NE9	95.30	93.12	92.64

Percentage yield of formulations NE1 to NE9 by varying drug to lipid ratio was determined and is presented in Table. Highest drug content, Highest Entrapment efficiency observed for NE6 formulation.

Figure 2: Particle size of NE6 formulation

Figure 3: Zeta potential of NE6 formulation

Figure 4: In vitro dissolution studies of NE1-NE9 Ethosomes formulations in percentage

Ethosomal Gel Evalaution Parameters:

Table 4: Ethosomal Gel Evalaution Parameters

Formulation

Viscosity (cp)

Clarity

Homogeneity

Drug Content

NE6G1

5.8

42299

Excellent

98.14

NE6G2

5.92

66500

Satisfactory

97.32

Figure 5: Ex vivo permeation studies for Ethosomal gel with different concentrations of carbopol.

Figure 10: Peppas release kinetics

The prepared NE6G1 optimised 1% carbopol gel was subjected to the drug release kinetics and release mechanism. The formulations were studied by fitting the drug release time profile with the various equations such as Zero order, First order, Higuchi and Korsmeyer pappas. The data revealed a better fit to the Peppas model.

FTIR

Infrared studies were carried out to confirm the compatibility between the lipid, drug, and selected excipients. From the spectra it was observed that there was no major shifting, as well as, no loss of functional peaks between the spectra of the drug and drug-loaded Ethosomal gel. This indicated no interaction between the drug and other excipients.

SEM

Figure 14: Nifedipine NE6G1 optimised 1% carbopol transdermal Ethosomal gel

SEM studies showed that the Nifedipine - loaded Ethosomes transdermal gel had a spherical shape with a smooth surface as shown in Figure.

CONCLUSION:

Novel vesicular drug delivery systems (Ethosomes) offer more advantages as compared to conventional drug delivery systems. Moreover; they are non-invasive, non-irritant and offers better functionality. Ethosomal systems are novel lipid vesicular carriers containing a relatively high percentage of ethanol. These nanocarriers are especially designed for the efficient delivery of therapeutic agents with different physicochemical properties into deep skin layers and across the skin. Ethosomes were prepared by and optimized on the base of average vesicle size, %drug entrapment and drug release. The optimized formulation was further incorporated with gel base (Carbopol gel) and characterized for their viscosity, pH, % drug content and drug release study. Optimized formulation (NE6) of ethosome resulted in average vesicle size as 3.01 mm, zeta potential as -32.55 mv, and %EE as 97.63%. Prepared gel of optimized formulation viscosity was 42299 cps, pH was 5.8, % drug content was 98.14, and in vitro drug release found as 94.34% in 12 h, respectively. It can be concluded that prepared gel containing Nifedipine -loaded Ethosomal formulation was optimized and successfully formulated in the gel form can be of use for topical preparation. The data shows that Nifedipine Ethosomal gel provides sustained release profile as well as it is non-irritant in nature. Transdermal system offers complete bypass of first pass metabolism.

ACKNOWLEDGEMENT:

Thе Authors arе thankful to Management and Principal, Department of Pharmacy, Samskruti College of Pharmacy, Hyderabad, for extending the support to carry out the research work. Finally, the authors express their gratitude to the Sura Labs, Dilsukhnagar, Hyderabad, for providing research equipment and facilities.

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Received on 08.10.2022 Modified on 10.11.2022

Asian J. Pharm. Res. 2023; 13(2):77-80.

DOI: 10.52711/2231-5691.2023.00015