Preparation of topical folic acid gel and investigation the effects of different penetration enhancers on the drug permeation rate

Other Title(s)

تحضير حامض الفوليك على شكل جل موضعي و التحقق من تأثير محسنات النفاذية على درجة نفاذيته

Dissertant

al-Far, Usamah

Thesis advisor

Qurt, Muammal Salah al-Din
Malikiyah, Numan

University

Birzeit University

Faculty

Faculty of Science

University Country

Palestine (West Bank)

Degree

Master

Degree Date

2018

English Abstract

Folic acid is a B group component of vitamins and it plays role in the production and maturation of red blood cells normally.

It is available in the market as tablet dosage form and in combination with iron compounds and other B vitamins.

Folic acid (FA) seems to have skin regeneration properties and it can modulate DNA repair in UV-damaged skin by improving the skin elasticity and moisturizing, decreasing trans-epidermal water loss and skin roughness without any significant change of sebum secretion.

Topical FA preparations are promising due to the ease of application and acceptability by the patients, but they are not effective because they do not penetrate the skin well.

The aim of this thesis is to investigate the effects of some penetration enhancers on permeation of newly developed FA gel, as a model of semisolid topical dosage form.

In the first phase the experiment diffusion parameters of (0.1% w/w) Folic acid gel was specified and used as a reference control to measure the effects of different penetration enhancers on its permeability.

In the second phase a pig skin was used to test the permeation of Folic acid from the selected gel-penetration enhancer system.

Franz diffusion cell was used in this in-vitro study.

In the first phase the membrane was composed of natural eggshell membrane soaked in isopropyl Myristate.

The receiver is filled with phosphate buffer pH 7.4.

The donor compartment contained 5 g of gel.

In the second phase, pig skin obtained from 9- weeks female pig skin was used to separate the receiver and donor compartments.

Samples of 1 ml volume were taken from the phosphate buffer at the receiver compartment after the first hour, and every hour later on up to (7) hrs for each experimental sample.

FA was quantified by using HPLC at λ = 254 nm.

The solubility of folic acid was determined in acetate buffer pH 4.5 and in phosphate buffers with different pHs.

The highest solubility was found in phosphate buffer pH 7.4 with a value of 0.680g/100ml.

The compatibility of folic acid was tested with different excipients (Benzyl alcohol, Carbopol, IPM, Tween 20, PSE-15, SLS, IPA, and TEA) for three days at room temperature and at 40 ºC.

It was found that FA is compatible with all excipients except with Carbopol that causes precipitation.

The penetration enhancers (PE) under investigation were Benzyl alcohol, Tween 20, Sodium Lauryl Sulphate, PSE-15, IPM and IPA.

They were added in different concentrations to 0.1% FA gel in the donor compartment.

Diffusion parameters determined were cumulative amount, slope and intercept of cumulative amount which is plotted versus time, TL, D, P, and K.

The (ER) was used as criteria for selecting the best penetration enhancer.

The enhancement ratio has been found to increase in the order of: Benzyl alcohol (1%) > Benzyl alcohol (1%) + 20% IPA > Benzyl alcohol (1%) + 2% IPM> Benzyl alcohol (1%) + 30% IPA FA gel containing 0.1% folic acid and the selected penetration enhancer (Benzyl alcohol) showed significant higher enhancement ratio than other agent’s formulae.

The final gel formula with the optimal concentration of penetration enhancer was then tested for permeation through pig skin.

The API showed good penetration through the skin with a permeability coefficient of 0.005 cm/hr.

The diffusion parameters for FA gel through natural eggshell membrane and pig skin are summarized in the following Table: Comparison of Diffusion parameters for FA gel, containing benzyl alcohol 1% as both preservative and penetration enhancer through eggshell membrane and Pig Skin using Franz diffusion cell The stability of FA gel was tested by incubating the finished products in their final package (aluminum tubes) at different storage conditions i.e.

25 ± 2 °C / 60 % ± 5% RH, 30 C ± 2 °C / 60% ± 5% RH and 40 C ± 2 °C / 75% ± 5% RH.

Samples were tested after two weeks and six weeks for the content of FA (assay), physical appearance, pH, and viscosity.

FA 0.1% gel proved to be stable in all aspects for the period tested (6 weeks) at all storage conditions.

Main Subjects

Pharmacology

Topics

• Permeability

No. of Pages

119

Table of Contents

• APA
• MLA
• AMA

Language

English

Data Type

Arab Theses

Record ID

BIM-889343