Permeation Enhancer

PERMEATION
ENHANCER
And discussion of a research article
‫جامعة الزرقاء‬
‫كلية الصيدلة‬
‫عمر مهدي صالح سبتي‬
20209399
TDDSs
• Transdermal drug delivery systems (TDDSs) is a delivery system t
hat facilitate the passage of therapeutic quantities of drug substanc
es through the skin and into the general circulation for their syste
mic effects.
• In 1965, Stoughton first conceived of the percutaneous absorption

of drug substances.
• The first transdermal system, Transderm Scop ( Baxter), was app

roved by the Food and Drug Administration (FDA) in 1979 for pre
vention of nausea and vomiting associated with travel, particularly
at sea.
TDDSs
• For transdermal drug delivery, it is considered ideal for the drug to
migrate through the skin to the underlying blood supply without b
uild up in the dermal layers.
• This is in direct contrast to the types of topical dosage forms, in w

hich drug residence in the skin, the target organ, is desired.
• Transdermal Drug Delivery System (TDDS) shows promising resu

lts when compared with oral drug delivery system mainly by elimi
nating the first pass metabolism and by improving the bioavail
abity of drug.
Skin Structure
• The skin is composed of the stratum corneum (the outer layer), the living epi
dermis, and the dermis, which together provide the skin’s barrier layers to pen
etration by external agents
• Percutaneous absorption of a drug generally results from direct penetration of t

he drug through the stratum corneum, a 10- to 15-μm thick layer of flat, partial
ly desiccated non living tissue
• The rate of drug movement across this layer depends on its concentration in t
he vehicle, its aqueous solubility, and the oil– water partition coefficient bet
ween the stratum corneum and the vehicle.
• Substances with both aqueous and lipid solubility characteristics are good can
didates for diffusion through the stratum corneum, epidermis, and dermis.
Skin Structure
FACTORS AFFECTING
PERCUTANEOUS ABSORPTION
• Drug concentration
• The area of application
• Physicochemical properties of the drug
• Drugs molecular weight
• Hydration of the skin
• Duration of application
PERCUTANEOUS ABSORPTION
ENHANCERS
• There is great interest among pharmaceutical scientists to develop
chemical permeation enhancers and physical methods that can i
ncrease percutaneous absorption of therapeutic agents.
• CHEMICAL ENHANCERS, a chemical skin penetration enhanc

er increases skin permeability by reversibly damaging or altering t
he physicochemical nature of the stratum corneum to reduce its dif
fusional resistance
Optimisation of Alfuzosin Hyd
rochloride Organogels for Tra
nsdermal Delivery
Optimisation of Alfuzosin Hydrochloride
Organogels for Transdermal Delivery
This work was carried out by D. Prasanthi, Kuruva Jyothirmai1, P. K.

Lakshmi, and G. Pulla Reddy College of Pharmacy, Mehdipatnam,
Hyderabad – 500 028, India.
The purpose of present research was to prepare and optimise

Alfuzosin hydrochloride (AH) organogels for transdermal delivery
using box-behnken design
Organogels
• Organogels are the semi-solid preparations, in which an organic liquid
phase is immobilized by a three-dimensional network composed of self
assembled, intertwined gelator fibers. They are thermoreversible, visc
o-elastic, transparent, biocompatible and non-irritant.
• Organogel based products usage has been increased due to its easy
method of preparation and long term stability, they are able to
accommodate both hydrophilic and hydrophobic drugs within its gel str
ucture.
• The gelators which are used in the preparation of organogels may be

sorbitan esters, polysorbates, lecithin and pluronics, eudragits etc.
Alfuzocin Hydrochloride (AH)
Transdermal Delivery
• Alfuzosin Hydrochloride (AH) used in the treatment of Benign Prostate Hy
perplasia (BPH) was chosen as a model drug in the preparation of organog
els for transdermal delivery.
• AH is α-adrenoreceptor blocker whose oral bioavailability is 49% in fed co
nditions.
• Due to its low oral bioavailability an attempt has been made to overcome
the bioavailability problem by formulating organogel of AH for transderma
l delivery
• Box-behnken design is one of the response surface designs used to optimis
e the formulation. Four factors, three levels box-behnken design was appl
ied to study the affect of independent variables on dependendent variables
using design expert software version 9.0
Materials and Methods
• Alfuzosin Hydrochloride (AH)

• Soyaphosphotidyl choline (SPC)
• Span80, Tween80, Tween20 and isopropyl myristate
• Oleic acid
• Nerolidol
• Sunflower oil and palm oil.
Preparation of Organogels
• Organogels were prepared by fluid filled fiber mechanism, where
in three different types of gelling agents like soyalecithin, Twee
n80 and Span80: Tween80 (1:2) in the concentration range of 30-7
0% w/w were used.
• Apolar solvents like sunflower oil, palm oil and isopropyl myrista
te (IPM) were used to dissolve the gelling agents and permeation
enhancers like nerolidol, Tween20 and oleic acid were used in the
concentration of 2% w/w.
• The prepared organogels were evaluated for all the physicochemi

cal properties, in vitro diffusion, ex vivo permeation, skin irrit
ation and stability studies.
Preparation of Organogels
• Gelling agent was dissolved in the apolar solvent under continous

stirring on magnetic stirrer.
• Drug was dissolved in water and added to the above mixture drop
wise, under continous stirring.
• Spontaneous formation of organogel was observed within few min
utes [5,6,7]. The compositions of organogels are detailed in Tables
1 and 2, which are according to box-behnken design.
• In all the above formulations 1% w/w (100 mg) of drug (AH) diss
olved in 2% w/w water was added and the concentration of apolar
solvent as adjusted to give 10 g of gel.
Experimental design: Box-behnken
experimental design
• Box–Behnken statistical design was used to statistically opt
imize the formulation factors and evaluate main effects, int
eraction effects, and quadratic effects on the amount perme
ated in 24 h (Q24) and flux.
• A four factor, three level design matrix comprising of 29 ex

perimental runs was constructed.
• The independent and dependent variables were listed in Ta

ble 1.
Experimental design: Box-behnken
experimental design
Observed values
Results & Discussion
Results & Discussion
 Among the three permeation enhancers, Tween20 has shown

better permeation of drug into the skin compared with
nerolidol and oleic acid.
 OA20 (87.11% release) formulated using Tween20 as

permeation enhancer has shown better drug release compared
with OA28 (42.23% release) formulated using nerolidol and
OA15 (27.73% release) formulated using oleic acid as perme
ation enhancers.
References
ALLEN, L. V., POPOVICH, N. G., ANSEL, H. C., & ANSEL, H. C. (2005). Ansel's pharmaceutical dosag
e forms and drug delivery systems. Philadelphia, Lippincott Williams & Wilkins.
Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincott illustrated reviews: Pharmacology (6th

ed.). Philadelphia, PA: Wolters Kluwer.
Prasanthi, D., Jyothirmai, K., & Lakshmi, P. K. (2016). Optimisation of Alfuzosin Hydrochloride Orga
nogels for Transdermal Delivery. Journal of Pharmaceutical Research International, 11(2), 1-16. htt
ps://doi.org/10.9734/BJPR/2016/24433

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PERMEATION

• In 1965, Stoughton first conceived of the percutaneous absorption

• The first transdermal system, Transderm Scop ( Baxter), was app

• This is in direct contrast to the types of topical dosage forms, in w

• Transdermal Drug Delivery System (TDDS) shows promising resu

• Percutaneous absorption of a drug generally results from direct penetration of t

• CHEMICAL ENHANCERS, a chemical skin penetration enhanc

This work was carried out by D. Prasanthi, Kuruva Jyothirmai1, P. K.

The purpose of present research was to prepare and optimise

• The gelators which are used in the preparation of organogels may be

• Alfuzosin Hydrochloride (AH)

• The prepared organogels were evaluated for all the physicochemi

• Gelling agent was dissolved in the apolar solvent under continous

• A four factor, three level design matrix comprising of 29 ex

• The independent and dependent variables were listed in Ta

 Among the three permeation enhancers, Tween20 has shown

 OA20 (87.11% release) formulated using Tween20 as

Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincott illustrated reviews: Pharmacology (6th

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