INTRODUCTION:

In emerging, it is striking to note that there are significant differences in transdermal or transdermal drug delivery systems (TDDS) and transdermal therapeutic systems (TTS). A transdermal patch or transdermal drug delivery system is defined as a system specifically designed for skin application and designed to distribute the active ingredients or drugs across skin layers into systemic circulation and ultimately at receptor sites far from the targeted region^1,2.

Transdermal drug delivery system can be defined as drug delivery across the epidermis to obtain systemic results. The success of transdermal patches depends on their composition. Transdermal patches dominate drug delivery at a controlled rate through the proper mixing of hydrophilic and lipophilic polymers^3,4,5.

Transdermal patch basically communicates with the topical transport agent on healthy uninjured skin during closed confinement treatment of the tissue placed on the skin or during scheduled treatment. Transdermal Patch offers few advantages to standard dosage forms or controlled release systems. The Transdermal patch provides continuous drug release, avoiding first pass metabolism, improved patient endurance and avoidance of dose loss^6,7,8. It is not a current concept during drug delivery across the skin due to the formation of a few topics that are accessible over the years during local drug delivery and the system. However, due to the lack of bioavailability of those delivery systems was established it became very difficult to detect drug overload. A flexible drug delivery system can deliver a specific drug to the system cycle at a certain rate^9,10.

However, the concept of transdermal drug delivery system is not new at the moment but in the delivery of antiemetic drugs the use of this delivery system is a new concept⁸. As vomiting is a rare form of gastrointestinal tract dig that requires special medical attention. The course of oral treatment is not appropriate and parental treatment has several limitations and disadvantages. Therefore, it is necessary to emerge in order to investigate a possible pathway instead of skin, in particular, transdermal. However, conventional medicine, namely, antiemetic therapy has direct side effects. Therefore, it needed to be round about the safe, effective and timely delivery system. Therefore, it is recommended to provide an effective and reliable drug delivery system during the treatment of vomiting and nausea^11,12.

Ramosetron Hydrochloride is a crystalline white powder that dissolves in water and methanol. It is a 5-HT3 receptor antagonist. It activates its antiemetic properties by blocking serotonin at 5-HT3 receptors that travel to afferent vagal nerve endings in the intestinal mucosa. Ramosetron hydrochloride is a recently discriminated form of 5-hydroxy tryptamine type 3 (5-HT3) antagonists apparently with distinct antiemetic effects that differentiate between 5-HT3 receptor antagonists¹⁰. It is considered to be potent and a few studies have shown that it has a longer duration of action and less side effects compared with antiemetics¹³. Conventional Ramosetron hydrochloride tablets are available on the market but the important disadvantage of the tablet is that it does not indicate the immediate onset of the action required in the event of vomiting. Vomiting is one of the most common side effects of cancer treatment. The purpose of this study is to develop and evaluate the anti-emetic transdermal drug delivery system to provide a systemic release rapid onset of action.

Ramosetron Hydrochloride is a white crystalline powder soluble in water and methanol. Ramosetron is a 5-HT3 receptor antagonist. It exerts its antiemetic property by blocking of serotonin to 5-HT3 receptors present in the afferent vagal nerve-endings in the GI mucosa. Ramosetron hydrochloride is a new selective 5 hydroxytryptamine type 3 (5-HT3) receptor antagonists that reportedly has more potent antiemetic effects compared with other 5-HT3 receptor antagonists³. It undergoes hepatic first-pass metabolism. It is found to be more potent and various studies have shown that it is having longer duration of action and least unwanted side effects when compared to other antiemetics⁴. Its conventional tablets are available in the market but the major drawback of that is, tablet does not show the faster onset of action, which is required in case of emesis. Emesis is one of the side effects of cancer treatment and may happens with pregnant women hence our aim is to prepare rapidly dissolving film of Ramosetron hydrochloride for rapid relief in emesis.

MATERIALS AND METHODS:

Materials: Ramosetron Hydrochloride was obtained from the sigma Aldrich, Polyvinylpyrrolidone, Polyvinyl alcohol, HPMC, Ethyl cellulose, Polyethylene glycol 400, DMSO and methanol, All chemicals and reagents used were of analytical grade.

Methods:

Fourier Transform Infrared Spectroscopy (FTIR):

The specimen of pure Ramosetron HCl with SCMC and HPMC were prepared individually by mixing KBr later drying in hot air oven for around 1 hr. afterwards stay in desiccators prior to scan the spectra throughout the ranges of 4000 to 500 cm-1 by FTIR.

Preparation of transdermal patches:

Ramosetron hydrochloride loaded matrix-type transdermal patches were prepared by solvent casting method. The polymers were accurately measured and dissolved in 10 mL of water and methanol in a 1: 1 ratio to form a clear solution. The drug was soluble in solvent and held until a clear solution was obtained. Polyethylene glycol 400 was used as a plasticizer and DMSO was used as an penetration enhancer. The solution was poured into a petri plate, lubricated with glycerin and allowed to stand at room temperature for 24 hours. A glass plate was placed on top of the petri dish to stop the rapid evaporation of the solvent. After 24 hours, the dried patches are removed and stored in a dry place for further evaluation¹⁴.

Evaluation of formulated patch:

Organoleptic parameters like colour, clarity, flexibility, appearance^15,16, weight variation, Thickness, Folding endurance, percentage moisture loss, Percentage moisture uptake and drug content were performed as per standard methods^17-25.

In- vitro drug release studies:

Using Franz diffusion cell in- vitro release studies were carried out. The transdermal patch was placed in the donor section and it was differentiated along with the receptor section by semi-permeable membrane. The recipient section contains 20 ml of phosphate buffer solution of pH 7.4 & 20% v/v of PEG-400, speed is maintained at 500 rpm and temperature at 37 ± 0.5^oC. One ml of sample was removed at pre-planned time durations. The drug content in the specimen was checked by UV-visible spectrophotometer at 241 nm and Drug release was calculated. ^26,27.

RESULT AND DISCUSSION:

The spectrum of UV was analyzed by UV-Visible spectroscopy and λmax found to be 241 nm with R2 value of 0.9913.

Fig. 1: Calibration curve of Ramosetron Hydrochloride in methanol

Drug-excipients interaction study:

The FTIR study manifests no physical or chemical interactions of Ramosetron hydrochloride with PVP, ethyl cellulose and SCMC as shown in Figure 6.

Fig 2: FT-IR spectra of pure drug Ramosetron Hydrochloride

Fig 3: FT-IR spectra of PVP

Fig 4: FT-IR spectra of SCMC

Fig 5: FT-IR spectra of Ethyl cellulose

Fig.6: FTIR spectra of physical mixture (Drug +SCMC+PVP)

Physical evaluation of Patch:

All the prepared polymeric Ramosetron Hydrochloride patches were characterized and results are summarized in table 1.

Table 1: Physical examination of patches

Batch	Stickiness	Flexibility	Transparency	Smoothness
F1	Non- Sticky	Flexible	Opaque	Smooth
F2	Non- Sticky	Flexible	Opaque	Smooth
F3	Non- Sticky	Flexible	Opaque	Smooth
F4	Non- Sticky	Flexible	Opaque	Smooth
F5	Non- Sticky	Flexible	Opaque	Smooth

Weight variation, thickness, drug content and folding endurance:

The physicochemical parameters such as weight variation, thickness, drug content and folding endurance of the transdermal patches are shown in Table 2.

Table 2: Evaluation parameters of Ramosetron Hydrochloride transdermal patch

Batch	Folding Endurance	Drug Content (%)	Thickness	Weight Variation
F1	89±2	35.98±1.6	0.41±0.74	156.5±1.85
F2	91±4	34.84±1.3	0.47±0.34	151.7±0.34
F3	96±8	37.56±1.9	0.51±0.47	159.3±0.67
F4	94±5	36.93±2.1	0.43±0.99	153.6±0.23
F5	93±9	33.34±1.4	0.57±0.12	157.5±0.65

Moisture absorption and moisture content studies:

The effect of moisture content and moisture absorption studies were shown in Figure 6 and table 3. The moisture content in the preparation differs from 10.34% to 15.56%. The moisture absorption in the preparation was from 19.01% to 26.86%.

Table 3: Moisture studies of transdermal patches

Batch	Moisture Content (%)	Moisture Absorbed (%)
F1	14.05	23.43
F2	12.65	26.86
F3	15.56	21.05
F4	11.00	19.01
F5	10.34	25.34

Fig.7: Moisture studies of transdermal patches

Mechanical properties:

Optimized preparation F3 manifested TS and EM values (2.66±0.027kg/ mm² and 7.19±0.06kg/mm²).

Table 4: Mechanical properties of transdermal patches

Batch	Tensile strength (kg/mm²)	Elastic Module (kg/mm²)	Elongation Break (%mm²)	Strain
F1	2.23±0.046	8.98±0.04	13.05±0.32	0.25±0.05
F2	2.69±0.019	7.23±0.07	15.86±0.43	0.35±0.07
F3	2.66±0.027	7.19±0.06	16.06±0.36	0.44±0.02
F4	3.24±0.198	6.45±0.56	14.65±0.76	0.37±0.01
F5	2.59±0.036	7.23±0.05	16.85±0.23	0.38±0.06

In- vitro drug release studies:

The drug release account of formulated transdermal films is given in Figure 8 and Table 5. The release studies manifest that F3 batch preparation has greater drug release 89.43 % in 8 hrs.

Table 5: In-vitro drug release study

Time (Hrs)	F1	F2	F3	F4	F5
0	0	0	0	0	0
0.5	28.50 %	33.62 %	36.45 %	31.56 %	29.96 %
1	31.65 %	44.89 %	47.98 %	42.51 %	33.56 %
2	34.89 %	59.61 %	60.56 %	54.69 %	38.45 %
4	38.34 %	66.54 %	68.23 %	63.93 %	47.32 %
6	40.54 %	71.24 %	73.87 %	68.42 %	59.45 %
8	43.59 %	83.12 %	89.43 %	81.34 %	68.39 %

Fig. 8: In-vitro drug release studies of transdermal patches

SUMMARY AND CONCLUDSION:

Ramosetron hydrochloride was successfully fabricated as sustained and controlled release transdermal patches and also shows that route of administration are beneficial and have better patient compliance. The all evaluation parameters results of the formulas were found to be in acceptable range. It may be concluded that the experiment of preparation and characterization of the Ramosetron hydrochloride patches was considered to be prosperous in the release of drug for an elongated interval of time, based on the observations.

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Received on 29.03.2022 Modified on 11.05.2022

Research J. Pharm. and Tech 2023; 16(7):3321-3325.

DOI: 10.52711/0974-360X.2023.00548