NOVEL FORMULATION STRATAGEM COMPRISING POLYPHENOL AS ADJUVANT IN THE MANAGEMENT OF ACNE VULGARIS
IN-VITRO DRUG RELEASE
ABSTRACT
PREFORMULATION STUDIES (a)
80
% cumulative release
70 60 50 40 30 20 10 0 0
1
2
3
4
5
6
7
8
9
70 60 50 40 30 20 10 0
10
0
Time (hrs)
1
2
3
4
5
6
7
8
9
Time (hrs)
(c)
PREPARATION OF NANOEMULSION
80
% Cumulative release
• Standard calibration curve for adapalene, resveratrol and benzoyl peroxide • Solubility studies (adapalene and resveratrol was determined by the shake flask method) • DSC and FTIR was carried out in order to determine compatibility
% Cumulative release
Introduction: Acne vulgaris is a common skin condition which is experienced by every people. According to GDB(Global Burden of Disease) study, about 85% of the population are being effected. Even though, it is not a life threatening disease, it affects the self esteem of people. Aim and objective: To treat acne with the help of first line drug and a flavonoid by implementing nanotechnology. Method: Spontaneous emulsification technique was employed for preparation of nanoemulsion. Further, in-vitro characterization and in-vivo studies was done. Result and conclusion: Cumulative drug release was more for marketed formulation. Whereas, the efficacy was more for prepared formulation compared to marketed one because of the flavonoid. Thus, we can say that the formulation has exhibited a synergistic activity and will be an effective on in the management of acne vulgaris.
(b)
80
70 60 50 40 30 20 10 0 0
1
2
3
4
5
6
7
8
9
Time (hrs)
• Nanoemulsion was prepared by mixing of oil, water, surfactant and cosurfactant using spontaneous emulsification method • Drug and flavonoid was dissolved in combination of oil and added to smix • Later it was titrated with water
(a) Prepared formulation – 70% of adapalene, 56% of reseveratrol (b)Prepared formulation- 69% of adapalene , 65% of resveratrol (c) Marketed product- 71% of adapalene, 73% of benzoyl peroxide
INTRODUCTION Low level of linoleic acid, MUFAs and lipoperoxides
CHARACTERIZATION OF OBTAINED NANOEMULSION
Additional factors responsible for acne
Smoking
Environment
Drugs
Genes
Immunity
INVIVO STUDIES • • • •
Stress
1.Hyperproliferation of follicular epithelium
Zeta Sizer was employed Particle size or globule size Polydispersity index (to determine the nature of distribution of particles) Zeta potential analysis (to determine charge of the particle)
ACNE VULGARIS Epidermis layer of the Skin
2. Hyper seborrhea from sebaceous gland
Triglycerides from sebum broken down into fatty acids by p.acne
3. P.acne
After
• Carbopol 934 was used as a gelling agent • It was dissolved in water and neutralized with triethanolamine
CHARACTERIZATION OF DRUG LOADED NANOEMULSION GEL
Dermis Layer of the Skin with Sebaceous gland
• • • •
SEBACEOUS GLAND P.acne leads to the activation of TLRs and releases
Before
Control group
Hormones, EGFR and, perilipins
Reacts with sebum
Sample
FORMULATION OF NANO GEL
Inflammatory mediators Inflammatory mediators are released
Skin irritation study
Determination of pH (Digital pH meter) Measurement of spreadability Viscosity (digital viscometer) Extrudability
Inflammatory cytokines like: IL-a, IL-8, TNF-a, IL-6 and IL-12
ADA+5mg RES
ADA+10mg RES
INVITRO AND INVIVO STUDIES • • • •
In this work we hypothsised to use flavanoid as an adjuvant along with adapalene. Nanotechnology has been incorporated in this study along with combination therapy in order to improve the permeation of the drug as well as to improve the effectiveness of the treatment.
In-vitro drug release Skin irritation study Induction of pustules Treatment of pustules induced animals
In-vivo efficacy studies Before
After
Treatment days
Prepared nanoemulgel (5mg resveratrol)
RESULTS 1.Solubility studies:
MATERIALS AND METHODS MATERIALS Materials: Adapalene was used as drug and resveratrol was used as flavonoid
EXPERIMENTAL DESIGN PREFORMULATION STUDIES PREPARATION OF NANOEMULSION CHARACTERIZATION FORMULATION OF NANO GEL IN-VITRO STUDIES IN -VIVIO STUDIES
\
Adapalene (mg/ml)
Resveratrol (mg/ml)
(Mean ± SD)
(Mean ± SD)
Oleic acid
0.10 ± 0.120
2.1 ± 0.291
Soya bean oil
0.11 ± 0.126
2.3 ± 0.216
Olive oil
0.13 ± 0.131
2.5 ± 0.032
Capmul MCM
0.14 ± 0.134
2.6 ± 0.160
Labrafil
0.20 ± 0.142
2.9 ± 0.152
Labrfac
0.21 ± 0.146
3.8 ± 0.122
Isopropyl myristate
0.25 ± 0.158
5.2 ± 0.340
Castor oil
0.26 ± 0.162
6.9 ± 0.294
Capryol 90
0.38 ± 0.181
45 ± 0.375
Tea tree oil
1.00 ± 0.250
10 ± 0.264
Capryol 90+ tea tree oil
0.40 ± 0.195
12 ± 0.540
Oil
12 days
Prepared nanoemulgel (10mg resveratrol)
11 days
Marketed formulation (Acnovate)
26 days
CONCLUSION: The prepared formulation had more efficacy than the marketed formulation. Thus, we can say that the formulation has exhibited its synergistic activity on combining with a polyphenol. Hence, we can conclude that the novel formulation containing adapalene and resveratrol served as a better candidate for the management of acne (pustules). Further studies are required to confirm the same.
REFERENCE: (a) S.K. Janani, Raman Sureshkumar, Sai Surya Nikitha Upadhyayula, et al. Will the polyphenol and adapalene combination be a good strategy on acne vulgaris?. Medical Hypotheses.2019, 133. (b) John J. Docherty, Heather A. McEwen, Thomas J. Sweet, et al. Resveratrol inhibition of Propionibacterium acnes. Journal of Antimicrobial Chemotherapy. 2007: 59, 1182–1184. (c) Muhammad ubaid, Sadaf ilyas ,et al. Formulation and in vitro evaluation of carbopol 934-based modified clotrimazole gel for topical application. An Acad Bras Cienc 2016 Oct- Dec; 88(4): 2303-2317.