INTRODUCTION:

Niosomes (NS) are cholesterol-stabilized vesicles formed by hydrating synthetic non-ionic surfactants¹. Cefpodoxime Proxetil (CDP) is a third-generation antibiotic used to treat Infections of the respiratory and urinary tracts, skin and skin structure, and gonorrhoea are all susceptible Gram-positive and Gram-negative bacteria. The absorption of CDP pills from the intestines is 50 %². Oral suspension, on the other hand, absorbs better than solid orals. Nonionic surfactants stabilised with cholesterol are used to make NS, which prevents the contents from leaking out of the vesicle³.

Particle size, shape, consistency in drug content, entrapment efficiency, and in vitro drug release were all assessed using spans and cholesterol.

MATERIALS AND METHODS:

Materials:

Cefpodoxime Proxetil was gifted from Akesiss Pharma Pvt Ltd, Bangalore, India. Span 40, 60 and 80, NaOH₂, Sodium dihydrogen Phosphate, Methanol, Diethyl ether were of Loba chemicals Pvt. Ltd. Hyderabad, India. Double distilled water was used throughout the process.

Methodology:

Identification of the drug:

The procured CDP was analysed for its purity and identity

Melting point:

A sharp melting point indicates the CDP's purity, while a lowered value indicates the presence of foreign elements. A digital melting point apparatus was used to determine⁴ the melting point of CDP.

λ_max of Cefpodoxime Proxetil:

Using a double beam UV spectrophotometer, the maximum concentration of CDP in 0.1N HCl was determined in the dilution range of 2-10g/ml⁵.

Solubility:

The solubility of CDP in the aqueous phase is critical for its dissolution and availability in the bloodstream for activity. CDP solubility was determined in 0.1N HCl, water, methanol, ethanol, and pH 7.4 PBS⁶.

Partition coefficient of Cefpodoxime Proxetil:

CDP’s partition coefficient in n-octanol-water was attained⁷.

Physical drug excipient compatibility:

CDP was subjected to DSC studies to find the interaction with excipients used.

Preparation of NS by modified Ether injection method:

Cholesterol and span 40/60/80 were dissolved in a mixture of 5mL diethyl ether and 2mL methanol containing a weighed amount of CDP. The succeeding solution was progressively injected into 10ml of hydrating solution phosphate buffer (PBS) at pH 7.4 using a micro syringe at a rate of 1ml/min. At 60±2^oC, the solution was continuously stirred using a magnetic stirrer. This results in vesiculation and the production of NS⁸. Several batches of NS were created in order to find the best formula. Table 1 depicted the components of NS.

Table 1: Composition of various NS

Ingredients	Formulations
Ingredients	CN-1	CN-2	CN-3	CN-4	CN-5	CN-6
Cefpodoxime Proxetil	200	200	200	200	200	200
Span 40	100	200	-	-	-	-
Span 60	-	-	100	200	-	-
Span 80	-	-	-	-	100	200
Cholesterol	200	200	200	200	200	200
Methanol	2	2	2	2	2	2
Diethyl ether	5	5	5	5	5	5
Phosphate buffer-pH 7.4 (ml)	10	10	10	10	10	10

Characterization of Niosomes:

Vesicle diameter:

The average vesicular diameter of 100 NS of all batches was determined using an optical microscope with a calibrated ocular micrometre⁹.

Percentage Cefpodoxime Proxetil trap:

Dialysis was used to test the entrapped CDP formulations. The niosomal dispersion in the dialysis bag was placed in a beaker with 400ml of 0.1N HCl, then the beaker was placed on a magnetic stirrer and operated at a speed of 10020rpm for 4 hours. After that, a double beam UV spectrophotometer was used to look for un-entrapped CDP in the solution inside the receptor compartment at 235nm. The CDP entrapment is calculated as the difference between the total quantity of drug added and the amount of un-entrapped drug identified divided by the total amount of drug added¹⁰.

Drug content:

In a 100ml volumetric flask, a suspension of NS equivalent to 200mg of CDP was obtained, which was dissolved and the volume increased to 100ml with 0.1N HCl. The percentage of content was measured at 235nm using a double beam UV spectrophotometer after 1ml of this mixture was diluted to 10ml with 0.1N HCl¹¹.

In-vitro Drug release:

The membrane diffusion technique was used to determine the release of CDP from NS formulations. A Dialysis membrane with a diameter of 2.5cm and an effective length of 8cm was used to keep the NS formulation equivalent to 200mg of CDP (donor compartment). In a beaker containing 100ml of 0.1N HCl, the membrane was inserted (receptor compartment). The entire assembly was positioned so that the lower end of the membrane carrying a suspension was just touching (1-2mm deep) the diffusion medium's surface. The temperature of the receptor media was kept at 37⁰.5°C and the magnetic stirrer was used to agitate it at 100rpm. At regular intervals, aliquots of 5ml material were taken and sink conditions were maintained. In a Double beam UV-VIS spectrophotometer, the obtained samples were analysed at 235nm with 0.1N HCl as a blank^12,13.

RESULTS AND DISCUSSION:

Melting point of Cefpodoxime Proxetil:

The melting of CDP is as described in the monograph, it was observed as 149.6±1.4°C.

λ_max of Cefpodoxime Proxetil:

The λ_max of CDP was established as 235 nm, promises its official standards and shown in in Fig.1.

Solubility of Cefpodoxime Proxetil:

When the solubility of pure CDP was compared to that of its standard, it was discovered that CDP has a high solubility in methanol (95%) but is essentially insoluble in water.

Partition coefficient of Cefpodoxime Proxetil:

The partition coefficient of CDP was found to be 3.5, indicating that it is nearly insoluble in water and has a strong affinity for lipids. As a result, for effective delivery, this can be implemented into NS.

Fig. 1: Calibration curve of Cefpodoxime Proxetil

DSC studies:

For the CDP and physical blend, DSC points were obtained. The thermal grammes of CDP with excipient blend migrated to the left, suggesting proper impregnation of CDP with excipients and no negative indicators.

Characterization of niosomes:

In triplicates, the drug content of all NS formulations was determined. The dialysis tube method was used to investigate the in vitro release of CDP from NS. The particle size was calculated. Following all of the characterizations, it was discovered that CN-4 was the best NS formulation among the others.

Size and size distribution:

The NS size was ranged between 0.04 to 0.56µm (fig.2).

Fig. 2: Morphology of niosomes

Entrapment efficiency

The entrapment efficacy was ranged from 78.29±2.5 to 89.63±1.4%. Formulation CN-4 has the highest entrapment efficiency (fig.3) compared to other formulations.

Fig. 3: Entrapment efficacy of prepared niosomes

Drug content:

The amount of CDP present in the formulations was in the range of 90.82±4.2 to 97.25±3.2% (table 2)

In vitro release:

Among the NS, F4 formulation has a highest percentage drug release and illustrated in fig.4.

Fig. 4: In vitro release comparison curve of all formulations

Table 2: Characterization of Formulations by various Evaluation Methods

Formulation	Entrapment Efficacy (%)	Particle Size (µm)	Drug content	*In vitro* drug release
CN-1	78.29±2.5	0.56±0.04	97.25±3.2	94.25±2.84
CN-2	82.27±3.6	0.19±0.01	92.05±2.5	93.09±3.49
CN-3	84.19±5.4	0.29±0.01	93.45±3.5	95.57±2.75
CN-4	89.63±1.4	0.15±0.01	90.82±4.2	96.31±1.98
CN-5	86.36±3.2	0.36±0.01	96.58±5.5	99.52±3.25
CN-6	87.62±1.2	0.42±0.03	94.98±6.7	92.94±2.32

CONCLUSION:

The authors conclude that Cefpodoxime Proxetil can be manufactured as niosomes for an efficient medication release rate based on their extensive investigation.

ACKNOWLEDGEMENT:

The authors would like to thank Akesiss Pharma Pvt Ltd, Bangalore, India for providing the gift sample of Cefpodoxime Proxetil.

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Received on 16.10.2021 Modified on 08.12.2021

Asian J. Pharm. Tech. 2022; 12(2):109-112.

DOI: 10.52711/2231-5713.2022.00018