Formulation and Evaluation of Transdermal Patches Containing Metformin for the Management of Gestational Diabetes

Suryawanshi Sushmita C., Varade Gauri S., Wagh Vaishnavi V*., Chaudhari Sejal S., Prof. Yeole Kishor M.

DCS’s A R A College of Pharmacy, Nagaon, Dhule

 *Correspondence: waghvaishnavi2003@gmail.com

DOI: https://doi.org/10.71431/IJRPAS.2025.4507

INTRODUCTION

Transdermal Drug Delivery System

Skin, being the most extensive organ that receives one-third of the total blood supplied throughout the body, was not known to be a route of drug delivery for systemic drugs until the late 20th century. Over the last decade, the field of transdermal drug delivery has been gaining attention owing to its advantages over conventional oral dosage forms. The global transdermal drug delivery market is estimated to grow and reach approximately $95.57 billion by 2025.

Transdermal drug delivery systems offer several benefits because drugs administered are able to bypass hepatic first-pass metabolism and factors that alter pharmacokinetics in the gastrointestinal tract. This significantly improves systemic bioavailability with reduced risk of side effects associated with concentration. This generally improves patient compliance as it is easy and convenient to apply with a lesser dosing frequency, as the drug is released at a predetermined rate over a prolonged period. This delivery provides the constant drug release but it also allows the short biological half-life drug continuously and eliminates the pulsed entry into the blood circulation. The Transdermal drug delivery system designed by various methods such as transdermal patches include matrix, micro reservoir, reservoir, adhesive, and membrane matrix hybrid. Matrix type transdermal patches are most popular as they are easy to construct.

Advantages of transdermal patches are -

i) They can avoid gastrointestinal drug absorption difficulties covered by gastrointestinal pH, enzymatic activity and drug interaction with food, drink and other orally administration drug.

 ii) They can substitute for oral administration of medication when the route is unsuitable as with vomiting and diarrhea.

 iii) To avoid the first pass effect e.g. Transdermal Nitroglycerin.

v) They are noninvasive, avoiding the inconvenience of parenteral therapy.

 v) They provided extended therapy with a single application, improving compliance over other dosage forms requiring more frequent dose administration.

vi) The activity of drugs having a start half-life is extended through the reservoir of drug in the therapeutic delivery system and its controlled release.

vii) Drug therapy may be terminated rapidly by removal of the application from the surface of the skin.

Disadvantages are -

 i) Some patients7 develop contact dermatitis at the site of application from one or more of the system components, discontinuation. necessitating

 ii) Only potent drugs are suitable candidates for transdermal patch because of the natural

Types of transdermal patches

1. Single-layer Drug-in-Adhesive Patch

Description: The drug is directly incorporated into the adhesive layer that sticks to the skin.

Advantages: Simple design, thin, cost-effective.

2. Multi-layer Drug-in-Adhesive Patch

Description: Similar to the single-layer version but with multiple layers containing the drug, allowing for controlled or sustained release.

Advantages: Can achieve complex release profiles.

3. Reservoir Patch

Description: Contains a separate drug reservoir (a liquid or gel drug compartment), covered by a rate-controlling membrane and adhesive layer.

Advantages: Controlled drug release; better for potent drugs.

4. Matrix Patch (or Monolithic)

Description: Drug is embedded in a polymer matrix which controls its release.

Advantages: Simplified structure; steady drug release.

Components of transdermal patches

Polymer Matrix

The polymer controls the release of the drug from the device. The following criteria should

be satisfied for a polymer to be used in transdermal patches.

(a) Molecular weight, chemical functionality of the polymer should be such that the specific drug diffuses properly and gets released through it.

(b) The polymer should be stable.

(c) The polymer should be nontoxic

(d) The polymer should be easily of manufactured

(e) The polymer should be inexpensive

(f) The polymer and its deagration product must be non toxic or non-antagonistic to the host.

(g) Large amounts of the active agent are incorporated into it.

(II) Drug 

Drug solution in direct contact with release liner.

(III) Permeation Enhancer

(a) Solvent 

These compounds increase penetration possibly by swelling the polar pathway.

e.g.: Water alcohols–Methanol & ethanol, / Dimethyl acetemide Propylene glycol and Glycerol.

(b) Surfactants 

 The ability of a surfactant to alter penetration is a function of the polar head group and the hydrocarbon chain length.

(IV) Other excipients 

 Adhesives

The pressure sensitive adhesive can be positioned on device or in back of the device.

i) It should not be irritant

ii) It should be easily removed

iii) It should not leave an un washable residue on the skin

iv) It should have excellent contact with the skin.

v) Physical & chemical compatibility with the drug

vi) Permeation of drug should not affect.

(V) Liner

 Protect the patch during storage. The linear is removed prior to use.

(VI) Backing 

Protect the patch from the outer environment.

Gestational Diabetes

Gestational diabetes occurs when the placenta produces hormones that make the mother’s body insulin-resistant. If the pancreas can’t produce enough insulin to overcome this resistance, blood sugar levels rise.

While gestational diabetes isn't always preventable, you can greatly reduce your risk with the right lifestyle changes:

1. Maintain a Healthy Weight

2. Eat a Balanced Diet

3. Exercise Regularly

4. Monitor Blood Sugar (if at risk)

5. Stay Hydrated

6. Avoid Smoking and Alcohol

MATERIALS AND METHODS

Table No. 01 Ingredient

Table 2. Formulation of metformin transdermal patches

Procedure

Step 1: Preparation of PEG 400 and Propylene Glycol Solution

Take the required quantity of PEG 400 in a clean beaker. Add propylene glycol to it. Mix thoroughly. Place the beaker on a magnetic stirrer and stir the mixture for 30 minutes at room temperature to ensure uniform mixing.

Step 2: Preparation of HPMC, Glycerine, and Water Solution

In another beaker, take the desired amount of distilled water. Gradually add HPMC while continuously stirring to avoid lump formation. Allow the HPMC to hydrate fully (may take 10–15 minutes) Add glycerin to the hydrated HPMC solution. Place the solution on a magnetic stirrer and stir for 30 minutes to obtain a uniform viscous gel-like solution.

Step 3: Preparation of Metformin Drug Solution

In a separate beaker, take ethanol and distilled water in the required ratio. Add metformin HCl to this hydroalcoholic solution. Stir continuously until the drug is completely dissolved. Place the solution on a magnetic stirrer and stir for 30 minutes.

Step 4: Final Mixing

All three solutions are prepared and uniformly mixed First, add the PEG 400 + propylene glycol solution into the HPMC-glycerine solution slowly with continuous stirring. Then add the metformin drug solution into the above mixture Continue stirring the final mixture on a magnetic stirrer for an additional 30–45 minutes to ensure a homogenous polymeric drug solution.

Step 5: Casting the Patch

Pour the final homogeneous solution into a clean Petri dish or glass mold (lined with a backing membrane or release liner if desired). Allow the patch to dry at room temperature or in a hot air oven (below 40–45°C) for 24–48 hours until a dry, flexible film is formed. Carefully remove the film and cut into required size patches.

RESULT AND DISCUSSION

1. Physical Appearance: - Color of the patch is white, it is flexible, smooth and transparent.

2. Folding Endurance: - Patch did not bbreak, shows good flexibility.

3.  Moisture Content: - Moisture content was 3.5%, which is acceptable.

4. Solubility: - Easily soluble in buffer

In the above formulation of the transdermal patch containing metformin were formulated by various combination of polymers and plasticizer. These patches successfully undergo through the various evaluation parameters such as physical appearance, moisture content, folding endurance and solubility test. These patches were easily soluble in the phosphate buffer. The color of the patches is transparent. Patches had passed all the physical evaluation and there is no error or defect. Trial batches were conducted of drug in which first three batches were failed due to filming properties, drug crystallisation and drug content issue.

CONCLUSION

In this study, a transdermal patch formulation for metformin was successfully developed with the aim of exploring an alternative method of delivery for managing gestational diabetes. The formulation process utilized various excipients, including HPMC, PEG 400, propylene glycol, and glycerin, which were combined to create a flexible and stable patch. The evaluation of the physical properties, drug content, and folding endurance of the patch demonstrated promising results. While the preliminary findings suggest that the patch could offer a non-invasive alternative to oral metformin, further research is needed to fully evaluate its efficacy and safety, particularly through in-vitro permeation studies and clinical trials. This project provides a foundation for future exploration into transdermal drug delivery systems for gestational diabetes and potentially other conditions.

ACKNOWLEDGEMENT

In general, the most significant individuals to acknowledge in your acknowledgment are your research adviser, the principal professor in charge of your project or research, and any other academic supervisors who are directly involved in your research. Regardless of how many acknowledgements you have, use the singular heading.

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