INTRODUCTION:

Now-a-days about 70% of API (active pharmaceutical ingredient) are taken orally and results are found not to be as effective as desired. Transdermal drug delivery system (TDDS) emerged as a boon to achieve the desired effect utilizing skin as a site of application of drug delivering it directly to the systemic circulation. TDDS is different from other traditional topical delivery of drug by providing sustain delivery of drug along with reducing the intensity of action and thus reducing the side effects associated with oral delivery of drug. TDDS is self-contained, discrete dosage form and has advantages over other systems of drug administration which in turn leads to increase patient compliance.

Its ease of application and removal, non-invasive nature, drug permeation in predetermined rate, by passing hepatic metabolism thereby increased bioavailability of drug; all these factors make this system most suitable for systemic delivery of drug over long time periods.^1-3

Pseudoephedrine HCl (PEH) is a sympathomimetic drug belongs to phenethylamine and amphetamine chemical classes. It is used as a nasal/sinus decongestant and as a stimulant, or in higher and frequent doses as a wakefulness-promoting agent; therefore to avoid the systemic circulation, so as to overcome the hazardous effects of oral applications of drugs. PEH have a short half-life of 4-5 h. 20 mg of doses, therefore 3 to 4 times a day can be administered orally. However, side effects may occur due to frequent dosing; including hypotension, tachycardia, insomnia, and tremors. The main objective of this study was to formulate a PEH patch for transdermal administration.^4,5

The main aim of formulating TDDS is to increases the drug permeability by administering the drug directly into the systemic circulation through skin and thereby decreasing the retention and metabolism of the drug in the skin. The transdermal patches were formulated of by using various polymers, plasticizer, penetrant and solvent.

MATERIALS AND METHODS:

Pseudoephedrine HCl was fetched as a gift sample from pellets pharma limited, Pashamylaram, Telangana, India-502307. Hydroxy Propyl Methyl Cellulose (HPMC) and Poly Vinyl Pyrollidine (PVP) are purchased from SD fine-chem. Limited, world road Bangalore, India. Dibutyl phthalate, DMSO, Methanol purchased from LOBA CHEMIE Bangalore, Karnataka, India. All other chemicals were of analytical grade.

Formulation of Pseudoephedrine HCl Loaded Transdermal Patch^6,7

Formulations of matrix type PEH transdermal patches using different polymers with varying composition and ratios. HPMC and PVP are the choice of polymers used along with PEH by solvent casting technique; Methanol as solvent, Dibutyl Phthalate as plasticizer and DMSO penetration enhancer were used. The weighed quantity of polymers along with drug, plasticizer and permeation enhancer is dissolved in methanol to make a homogenized mixture followed by sonicating the mixture to avoid any lumps. A 5ml of homogenised solution was poured into Petriplate with glass ring wrapped with aluminium foil at bottom by adhesive with area of 23.75 cm². The petriplate is left for drying at room temperature for 24 hrs by keeping inverted funnel to facilitate the solvent evaporation at controlled rate. The dried films were cut into desired area (2.009 cm²) and stored in a desiccator till further used.

Table 01: Composition of various formulation

Sr. No.	ingredients	Formulations
Sr. No.	ingredients	F1	F2	F3	F4	F5	F6
1	Pseudoephedrine HCl	10	10	10	10	10	10
2	Hydroxy propyl methyl cellulose(mg)	0	50	100	150	200	300
3	Polyvinyl Pyrrolidone (mg)	300	250	200	150	100	0
4	DMSO (ml)	0.8	0.8	0.8	0.8	0.8	0.8
5	Dibutyl phthalate(ml)	2	2	2	2	2	2
6	Methanol(ml)	10	10	10	10	10	10

Characterization of PEH polymeric transdermal patch ^8-12

The medicated patches were evaluated for their physicochemical characteristics such as physical evaluation, weight variation, thickness, drug content, percentage moisture absorption, percentage moisture loss, folding endurance, in vitro drug release, in vitro drug permeation studies [.

Physical evaluation:

All the medicated patches were assessed for their physical characteristics; viz, smoothness, clarity brittleness were evaluated visually.

Weight variation:

randomly five patches were taken from every formulation for evaluation purpose. Uniformity of weight was determined by utilizing an analytical balance.

Thickness:

The micrometre screw gauze was used to determine thickness of the transdermal patches by keeping the transdermal patch as sandwiched between the two glass slides of known thickness. The thickness is measured at three different sides of the patch to get uniformity.

Surface pH:

The patches were allowed to swell by keeping them in contact with 0.5 ml of double distilled water for 1 hour in glass tubes. The surface pH was determined by using pH paper.

Folding endurance:

It is done manually by repeatedly folding at the patch at the same place till it broke. The number of times the patch could be folded without cracking/breaking gave the reading of the folding endurance.

Tensile strength:

The transdermal films were sandwiched individually by corked liner iron plates; where as one end is connected with a freely moveable thread over a pulley and the other one is kept fixed with the help of iron screen. The weight is added to the pan close with the hanging end of the thread. The elongation of the film is measured by pointer on the thread. The weight required to break the transdermal film is taken. the tensile strength was calculated using the following equation.

Tensile strength = Maximum applied force/Minimum cross-sectional area

= m × g / b × t kg / mm²

Where,

m- Mass in kg;

g- Acceleration due to gravity at 980 cm/sec

Drug content:

A film of required area was cut into small pieces and taken into a volumetric flask and dissolved in 100 ml water by keeping it on magnetic stirrer and rotating it till complete dissolving of the film. The solution was filtered and the suitable dilution is made then drug was determined spectroscopically at 210 nano meters.

Water vapor transmission studies:^13,14

Vials of equal diameter were used as a transmission cells. Transdermal patches were fixed to the brim of transmission cells containing one gram of fused calcium chloride with the help of adhesive film. The transmission cells were kept in a desiccator containing 200ml of potassium chloride after weighing accurately. Hygrometer was used to measure the inside relative humidity and found to be 80-90%. The cells were weighed after taking out at 2, 8, 12, 24, 48 and 72 hours. The water vapor transmitted was calculated by increase in the weight by using formula, water vapor transmitted rate= WL/S. where W= Gm of water transmitted, L= thickness of the patch and S= exposed surface area of the patch.

In vitro permeation study:

In vitro permeation study of medicated transdermal patches were done by using a modified Franz of diffusion cell. The semipermeable membrane was sandwiched between the donor and receptor compartment. The transdermal patch with aluminum foil acting as a backing membrane is kept in intimate contact with the membrane in such a manner that the backing membrane facing towards donor compartment whereas the transdermal patch towards receptor filled with phosphate buffer P^H 7.4. the diffusion cell content was continuously stirred with the help of magnetic stirrer throughout the experiment by maintaining temperature at 37℃±5℃. At fixed time of intervals 1ml receptor fluid is withdrawn and immediately replaced it by fresh fluid. The withdrawn fluid after suitable dilution were analyzed for drug content spectrophotometrically at 210nm.

Stability test:¹⁵

This was performed by keeping different temperature conditions for optimized formulation, so as to determine effects of various temperature conditions for the storage of formulation. Samples were analyzed after 3 months of storage at (freezer) 0°C ± 1°C, C (refrigerator) 8°C ±0.1°C, 25°C ± 0.1°C (incubator), and 40°C ± 0.1°C (incubator)⁵. All formulations were tested for changes in physical appearance, moisture contents, drugs contents and weight variations.

Table no. 02: organoleptic characteristics

Properties	Observed result	Result reported
Colour	White	White
Odour	Odour less	Odour less
Appearance	Crystalline powder	Crystalline powder
Melting point	182℃- 185℃	183℃±1℃

RESULTS AND DISCUSSION:

The transdermal preparation of PEH by solvent casting technique were found to be satisfactory. The prepared films were smooth, flexible, thin, transparent and had uniform surface indicating uniform dispersion of polymer throughout the transdermal film. The physicochemical evaluation data revels that there were no changes in physical appearance, flexibility and color when the films were stored at room temperature. To authenticate the method applied to prepare transdermal films furthermore the determination of thickness of the prepared patches was done and the result was found to be in the range of 0.242± 010-0.311±0.014mm which suggested that with least standard deviation and uniform thickness the employed method of preparation was found to be best result. From the data of surface pH it is evident that the formulations are free from skin irritation which is a major disadvantage of transdermal films is 7.4 which is almost equal to the pH of skin, the weight of the transdermal patches ranges from 20.56±0.30-24.73±0.16mg showing evident about the using of different polymers in different ratios will have effect on the weight as formulation F4 with least having both the HPMC and PVP in equal concentration with that formulation of F6 which have only HPMC in the highest concentration, it also contributes about the density of polymer will also have its role in weight variation, when it comes to folding endurance the data revels that F2 have the least ( 111±10.00) and F6 has the maximum ( 188±10.45), it may be due to that the films prepared with only HPMC polymer are smooth thin and elastic in nature than other formulation which is prepared in combination with PVP. This results get even evident with the data from tensile strength which also indicates that F6 has maximum (1.70±0.02) compared to other formulations. The WVTR was least for F1 (0.1256) and highest for F6 (0.1384). this data justifies that HPMC is more hydrophilic than the PVP. The results of in vitro release study (Table no.: 3) shows that the formulation F6 have maximum release with flux of 28.23±1.202 with least for formulation F1 16.56±1.201. As PEH is soluble in water and HPMC is hydrophilic in nature which facilitated the drug release along with the permeation enhancer and plasticizer; DMSO also emerged as a bets permeation enhancer by facilitating the release of drug from the transdermal patch.

The optimized formulation F6 was further subjected to stability studies at various temperature to check the stability of the transdermal films in different climatic conditions; results reveals that there are no changes in physical appearance, weight and drug content along with folding endurance and tensile strength of the formulations suggesting that the F6 can withstand different climatic condition without any change in their physicochemical properties.

Table no.03: Physicochemical data of prepared transdermal films

Formulations	F1	F2	F3	F4	F5	F6
Thickness (mm)n=5	0.287±0.018	0.242±0.010	0.254±0.016	0.2460±0.017	0.311±0.014	0.302±0.010
Surface PHn=5	6.58±0.05	6.54±0.04	6.52±0.03	6.48±0.09	6.49±0.09	6.59±0.02
Weight variation (mg)n=5	21.04±0.32	24.32±0.21	21.08±0.16	20.56±0.30	24.59±0.27	24.73±0.16
Folding endurancen=5	144±10.43	111±10.00	168±11.20	156±10.02	118±11.21	188±10.45
Tensile strength (kg/cm²) n=5	1.159±0.02	1.162±0.03	1.163±0.05	1.166±0.04	1.168±0.02	1.70±0.02
WVTR(gm/cm²/72hrs)	0.1256	0.1248	0.1312	0.1361	0.1325	0.1384
Drug content (%) n=3	98.38±0.28	98.02±0.34	98.45±0.54	97.23±0.34	98.56±0.56	99.10±0.21
Flux(µg/ cm²/hr)	16.56±1.201	20.89±1.802	14.62±1.302	18.28±1.207	10.14±1.506	28.23±1.202

CONCLUSION:

The research work has been done to study the feasibility to formulate PEH in transdermal films by using HPMC and PVP as polymers alone and in combination. The physicochemical evaluation data for various parameters helps in understanding the suitability of PEH as a model of drug and HPMC and PVP as polymers. It is proved from the study that the films prepared with HPMC has good folding endurance, tensile strength, WVTR and moreover in vitro drug release. The transdermal films prepared with HPMC alone has satisfactory in vitro release suggesting the suitability of PEH to formulate as transdermal films by using above suggested polymers. Considering the research work data polymer based transdermal patches containing PEH can emerged out as an efficient delivery system which when applied to the skin can deliver drug in control manner for prolonged period of time directly into the systemic circulation; thereby bypassing the hepatic metabolism of drug and reduces the dosing frequency which in turn reduces the side effects associated with frequent dosing.

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Received on 23.10.2021 Modified on 17.03.2022

Res. J. Pharma. Dosage Forms and Tech.2022; 14(3):195-198.

DOI: 10.52711/0975-4377.2022.00031