Formulation And Evaluation of Transdermal Patches of Doxycycline for Acne

Transdermal Drug Delivery System (TDDS) is a modern and innovative method of delivering therapeutic agents through the skin directly into the systemic circulation. Unlike oral or injectable routes, TDDS offers numerous advantages such as avoiding gastrointestinal disturbances, bypassing hepatic first-pass metabolism, and enabling sustained and controlled drug release over extended period⁽¹⁾. This method enhances bioavailability, reduces dosing frequency, and improves patient compliance, especially in chronic treatments. The skin, particularly the stratum corneum, acts as a barrier to drug entry⁽²⁾. However, advances in formulation science—such as the use of penetration enhancers, liposomes, pro-drugs, and polymeric matrices—have made it possible to overcome this barrier efficiently. The system generally consists of components like a drug reservoir, adhesive layer, backing membrane, and release liner, each contributing to the effectiveness and safety of drug delivery⁽³⁾. Historically, topical creams and ointments were the main approaches for dermatological conditions. With technological advancements, transdermal patches emerged in the 1980s and 1990s and have since become a reliable means of drug delivery⁽⁴⁾. including treatments for cardiovascular diseases, hormone therapy, and dermatological conditions like acne. For instance, in the case of acne vulgaris, antibiotics like doxycycline can be incorporated into a transdermal patch⁽⁵⁾. This localized delivery reduces systemic side effects and increases therapeutic efficiency by targeting the affected skin directly, making it a promising option in the field of dermatology.Thus, TDDS represents a significant advancement in pharmaceutical technology, offering a patient-friendly, effective, and targeted method of drug delivery⁽⁶⁾.

MATERIAL AND METHOD:

Materials required:

Doxycycline, HPMC, propylene glyacol, glycerin, Ethanol

Methodology:

1.Polymer Dissolution: Accurately weigh the required amount of HPMC polymer. Dissolve it in a mixture of ethanol and acetone (usually 1:1 ratio) under continuous stirring using a magnetic stirrer⁽⁷⁾. Stir the solution gently to avoid bubble formation. Continue stirring until a clear, homogeneous polymer solution is formed⁽⁸⁾.

b. Drug Incorporation: Weigh the accurate amount of doxycycline. Dissolve the doxycycline separately in a small amount of ethanol to ensure complete solubilization⁽⁹⁾. Add the drug solution slowly into the polymer solution under continuous stirring⁽¹⁰⁾.

c. Addition of Plasticizer: Add an appropriate amount of propylene glycol (usually 10-30% w/w of the polymer weight) as a plasticizer into the solution.Stir continuously to achieve a uniform mixture⁽¹¹⁾.

2. Casting of the Film

a. Preparation of Casting Surface: Clean and dry Petri dishes (or glass molds). If needed, lightly lubricate the surface with a few drops of glycerin to facilitate easy removal of the film (optional)⁽¹²⁾.

b. Pouring the Solution :Carefully pour the prepared solution into the Petri dish. Spread uniformly to ensure even thickness across the dish. (You can gently rotate the dish for uniform spreading.)⁽¹³⁾.

c. Drying : Allow the solvent to evaporate at room temperature for 24–48 hours in a dust-free environment. Alternatively, drying can be accelerated by placing the dish in a hot air oven at a low temperature (not exceeding 40–45°C) to prevent degradation of doxycycline⁽¹⁴⁾.

3.Removal of the Patch

Once dried completely, carefully peel off the film from the Petri dish using a spatula or tweezers⁽¹⁵⁾.

4.Cutting and Storage

Cut the dried film into patches of desired size (e.g., 2 cm × 2 cm or as required). Wrap the patches in butter paper or aluminum foil and store them in a desiccator or an airtight container until further evaluation⁽¹⁶⁾.

Formulation table : ⁽¹⁷⁾

Evaluation test :

5. Identification and characterization of drug

1.Organoleptic Properties:

Appearance: Yellow crystalline powder

Odor:  Odorless

Taste: Bitter⁽¹⁸⁾

b. Melting Point:170 -190°C

c. Solubility:

Soluble in water and methanol

Slightly soluble in ethanol

Practically insoluble in ether and chloroform⁽¹⁹⁾

2. Characterization:

a.Particle Size Analysis:

Important for drug release rate from the patch.

b. pKa and LogP:

pKa ~ 3.3 and 9.4 (two ionizable groups)

LogP ~ -0.2 to 0.5 (indicating moderate hydrophilicity)⁽²⁰⁾

5. UV spectroscopy :

UV-Visible spectroscopy, with a λmax around 270–280 nm, is commonly used to measure drug content and permeation in transdermal patches due to its accuracy and cost-effectiveness⁽²¹⁾. A standard drug solution is prepared, diluted to 2–20 µg/mL, and absorbance is measured at λmax. A calibration curve is then plotted with absorbance versus concentration⁽²²⁾.

5. IR spectroscopy:

FTIR spectroscopy is used to analyze chemical interactions and compatibility between drugs and excipients in transdermal formulations. Pellets of pure drug, polymer, and drug-loaded patch (each mixed with KBr) are scanned over 4000–400 cm?¹ using an FTIR spectrophotometer⁽²³⁾. The resulting spectra are compared to identify characteristic functional groups and confirm component compatibility⁽²⁴⁾

5. Weight uniformity :

Randomly select about 20 to 30 patches from a batch. Individually weigh each patch carefully ,Using an analytical balance (precision at least 0.1 mg).Record the weight of each patch⁽²⁵⁾.

5. Thickness:

Randomly select a few patches (typically3-5 samples) from the batch to ensure the Measurement is representative. Micrometer or Digital Caliper: Micrometer: This is ideal for precise measurements especially for thin patches like pimple Patches⁽²⁶⁾.

Digital Caliper: If a micrometer is not available a digital caliper with a high precision (0.01 Mm or better) can be used. Ensure the caliper is calibrated for accuracy⁽²⁷⁾.

5. Surface pH :

pH Meter: Place the pH probe gently on the surface of the patch (without pressing too hard). If needed, you can lightly moisten the patch surface with a small amount of distilled water(especially ifit’sa dry patch) before measurement⁽²⁸). This is done to improve contact with the probe and avoid affecting the patch’s structure.Record the pH from the meter’s display⁽²⁹⁾.

5. Percent moisture content :

Drying Oven or Desiccator: A drying oven is commonly used for accurate moisture content Measurement, but a desiccator can also work if lower temperatures are used⁽³⁰⁾.

5. Drug content :

Drug content evaluation involves sampling from a batch and analyzing the active ingredient using techniques like HPLC or UV-Visible Spectrophotometry. Content uniformity checks ensure consistent API distribution in individual units⁽³¹⁾. Dissolution tests assess drug release over time using USP apparatus, while stability testing monitors content under various conditions. Impurity and degradation analysis is also done using HPLC or GC, all following validated pharmacopeial standards⁽³²⁾.

5. Drug  solubility :

To evaluate drug solubility, a known excess amount of the drug is added to a fixed volume of Solvent (usually water or a buffer) in a sealed container^(33). The mixture is then stirred or shaken Continuously at a controlled temperature (typically 25°C or 37°C) for 24–48 hours to reach Equilibrium.⁽³³⁾

5. Dissolution Time :

Dissolution testing of a transdermal patch assesses drug release over time. A patch section is placed in USP Apparatus II with phosphate buffer (pH 7.4) at 32°C.⁽³⁴⁾ The paddle stirs at 50–100 rpm, and samples are collected at set intervals, then analyzed by UV spectrophotometry or HPLC. The resulting drug release profile helps evaluate release rate and patch performance⁽³⁵⁾.

Results :

5. Weight uniformity :

5. Thickness :

5. Surface pH:

5. Percent moisture content :

5. Dissolution Time:

5. Drug content :

5. Drug solubility :