Composition of Deriva Aqueous Gel

Active ingredient Adapalene Excepients Methyl paraben Phenoxyethanol Preservative Preservative 0.1% micro suspension

Propylene glycol

Emollient and moisturiser

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Deriva : Mechanism of Action

Adapalene (Deriva) has selective receptor binding activity thus providing an improved risk-benefit ratio in the treatment of acne with retinoids. Adapalene does not bind to cytosolic retinoic acid binding proteins (CRABPs) improved tolerance.
It activates only g and b subtype receptors and it has no effect on the RXRs Specificity to tackle terminal differentiation.
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Clinical Pharmacology
Adapalene is a modulator of cellular

differentiation, keratinization, and

inflammatory processes all of which

represent important features in the

pathology of acne vulgaris.
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Pharmacokinetics
The systemic levels of adapalene detected in man, after topical exposure, are low.
Adapalene is chemically and photo chemically stable. In contrast to the other retinoids, which, in the skin, can be inactivated or converted to other active compouds.

Adapalene is mostly metabolized into Odemethylated and hydroxylated derivatives.

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Adapalene
COOH

COOH

CH CH 3O 3O

Structure of adapalene
Functional group
Naphthoic acid
Adamantyl
CH3O

COOH

Property
Aromatic
Lipophilic

Consequences
Stable to light and oxygen
High levels in skin

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Contraindications
Hypersensitive to adapalene or any of the components in the vehicle gel.

Warnings
Patients with sunburn should be advised not to use the product until fully recovered.
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Precautions
Exposure to sunlight, including sun lamps, should be minimized during the use of adapalene. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided. Avoid contact with the eyes, lips, angles of the nose, and mucous membranes. The product should not be applied to cuts, abrasions, eczematous skin, or sunburned skin.
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Drug Interactions
Concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high

concentrations of alcohol, astringents, spices,

or lime) should be approached with caution.
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Carcinogenesis, Mutagenesis, Impairment of Fertility

In a series of in vivo and in vitro studies, adapalene did not exhibit mutagenic or genotoxic activities.

Pregnancy
Pregnancy category C.
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Precautions
Nursing Mothers
It is not known whether this drug is excreted in human milk.
Caution should be exercised when Deriva Aqueous Gel is administered to a nursing woman.

Paediatric Use
Safety and effectiveness in pediatric patients below the age of 12 have not been established. Sales Training

Adverse Reactions
Erythema, scaling, dryness, pruritus, and burning will occur in 10-40% of patients.
Pruritus or burning immediately after application may occur in approximately 20% of patients. 1% or less of patients: skin irritation, burning/stinging, erythema, sunburn, and acne flares.
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Dosage & Administration

Deriva Aqueous Gel should be applied once a day to affected areas after washing in the evening before retiring. During the early weeks of therapy, an apparent exacerbation of acne may occur. This is due to the action of the medication on previously unseen lesions and should not be considered a reason to discontinue therapy. Therapeutic results should be noticed after eight to twelve weeks of treatment.
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Indications & Usage

Deriva Aqueous Gel is indicated for the topical treatment of acne vulgaris; in Type I, II and III acne with comedones.

Presentation
Deriva Aqueous Gel is available in 15 gms tube with a package insert.
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Adapalene - Molecular Characteristics

Modulation of Differentiation
Due to both the affinity for the RARg receptors and the preferential localization of these receptors in cells undergoing terminal differentiation, Adapalene specifically acts on

keratinocyte terminal differentiation, which is

strongly disturbed in acne lesions.
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Adapalene - Molecular Characteristics

Lesser Skin Irritancy
The irritation potential of adapalene was found to be low, whether tested under occlusive or non-occlusive conditions on a variety of sites (face, chest, back and buttocks). Selective receptor binding activity for RARb and g and not for RARa, whereas tretinoin binds to all 3 subtypes. Also adapalene does not bind to CRABP.
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Adapalene - Molecular Characteristics

Lesser Skin Irritancy
Different molecular structure. In the case of tretinoin, a long chain organic acid, there could be non-specific interference with the cell membrane function, whereas Adapalene is a more neutral molecule. Adapalene is more stable chemically than tretinoin and does not break down in the presence of light as does tretinoin.
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Adapalene - Molecular Characteristics

Anti-proliferation Action Follicular epidermal hyperplasia is usually related to comedone formation.
Adapalene has an inhibitory activity on epidermal hyperplasia. This may be attributed to the lack of affinity for RARa.
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Adapalene - Molecular Characteristics

Skin Distribution and Follicular Penetration
Follicular penetration could be observed as
early as 5 minutes after application. After 2 hours microcrystals of Adapalene can be seen in the follicle to a depth of 400 m.
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Adapalene - Molecular Characteristics

Skin Distribution and Follicular Penetration
Owing to its lipophilic nature, adapalene will
dissolve readily into the sebum. Thus with adapalene, double targeting to its site of action viz. the follicle is possible due to its lipophilicity and appropriate particle size.
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Adapalene - Molecular Characteristics

Comedolytic effect
The reduction in the number of comedones
was found to be higher with adapalene (6070%) than with retinoic acid (30-50%).

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Adapalene - Molecular Characteristics

Anti-inflammatory Activity
Moderate to strong and comparable with reference to anti-inflammatory substances such as indomethacin and betamethasone - 17 - valerate. Largely superior to the reference retinoids tested such as tretinoin.

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Clinical Backup Adapalene 0.1% gel has low skin-irritation

potential
Michele Verschoore, MD et al (J Am Acad Dermatol 1997; 36: S104-9)

Conclusion
Adapalene 0.1% gel was significantly less irritating than tretinoin 0.025% gel.

Adapalene 0.1% gel has low skin irritation potential even when applied immediately after washing
Dunlap FE; Baker MD; Plott RT; Verschoore M (Br J Dermatol - 1998 Oct; 139 Suppl 52: 23-5)

Conclusion
It was concluded that application of adapalene gel 0.1% is well tolerated even when applied immediately after Sales Training washing.

Split-face comparison of adapalene 0.1% gel and tretinoin 0.025% gel in acne patients
Daniele Caron, et al (J Am Acad Dermatol 1997; 36: S110-2)

Clinical Backup

Conclusion
Adapalene 0.1% gel was significantly less irritating than tretinoin 0.025% gel when tested in acne patients. Adapalene 0.1% gel is better tolerated than tretinoin 0.025% gel in acne patients
Michele Verschoore, MD, et al (J Am Acad Dermatol 1997; 36: S116-8)

Conclusion
The results of these two multicenter clinical studies indicate that adapalene gel is better tolerated than Sales Training tretinoin gel.

Clinical A comparison of theBackup efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: A multicenter trial
A. Shalita, MD; J. S. Weiss MD (J Am Acad Dermatol 1996; 34: 482-5).

Conclusion
Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.
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Clinical Backup Clinical efficacy and safety comparison of

adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials
W. J. Cunliffe, MD, et al (J. Am Acad Dermatol 1997; 36: S126-34).

Conclusion
Adapalene 0.1% gel is a safe & effective treatment of acne vulgaris. Skin tolerance of adapalene 0.1% gel in combination with other topical antiacne treatments
Daniele Caron, PhD et al (J Am Acad Dermatol 1997; 36: S113-5).

Conclusion Under the conditions of the study, all tested treatments alone or in combination appeared nonirritating. Sales Training

Evaluation of clinial efficacy and safety of Clinical Backup adapalene 0.1% gel versus tretinoin 0.025% gel in the treatment of acne vulgaris, with particular reference to the onset of action and impact on quality of life
Grosshans E; Marks R; Mascaro JM; Torras H; Meynadier J; Alirezai M; Finlay AY; Soto P; Poncet M; Verschoore M; Clucas A (Br J Dermatol - Oct-1998; 139 Suppl 52: 26-33)

Conclusion

These differences appear to result in an earlier and greater quality of life improvement for the patients receiving adapalene.
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Clinical Backup Adapalene 0.1% gel for the treatment of acne vulgaris: its superiority compared to tretinoin 0.025% cream in skin tolerance and patient preference
Dunlap FE; Mills OH; Tuley MR; Baker MD; Plott RT (Br J Dermatol - Oct-1998; 139 Suppl 52: 17-22)

Conclusion This study showed that a majority of patients preferred adapalene 0.1% gel over tretinoin 0.025% cream and that it caused significantly less skin irritation.
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Clinical Backup Comparative tolerance of adapalene 0.1%

gel and six different tretinoin formulations
Galvin SA; Gilbert R; Baker M; Guibal F; Tuley MR (Br J Dermatol - Oct-1998; 139 Suppl 52: 32-40)

Conclusion The experimetnal results show that adapalene 0.1% gel is significantly better tolerated than any of six formulations of tretinoin, including two gels, three creams and a microsphere formulation, ranging in potency from 0.01% to 0.1%.
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Adapalene
After topical application, microparticles ranging from 3-10 m selectively penetrate the follicular ducts (which are the target sites in acne. Particles larger than 10 m remain on the skin surface. Particles smaller than 3 m are randomly distributed in the stratum corneum and hair follicles.
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Microsphere technology
Microsponge are polymeric delivery systems consisting of porous microspheres that can entrap a wide range of active ingredients, which can then be incorporated into many

product forms, such as creams & lotions

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Microsphere
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Rationale of Microsphere Technology

MS Technology Offers Increased efficacy for topically active agents Enhanced safety

Extended product stability

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Microsphere technology
Microspheres averaging 125 m in diameter act like microscopic sponges, storing the active drug until its release is triggered by application to the skin surface. Release of the drug into the skin is initiated by a variety of triggers, including rubbing and higher than ambient skin temperature.
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Microsphere technology
Absorption takes place in a time controlled manner that reduces the incidence and severity of skin irritation. Protects from photo degradation, therefore contributes to the long term stability of active ingredients In addition, the Microsphere formulation has been shown to reduce facial oiliness which can otherwise limit adherence to prescribed regimen
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Salient Features
Microsponge are polymeric delivery systems consisting of porous microspheres Microspheres are round microscopic particles made of synthetic polymer

Microspheres can entrap a wide range of active ingredients.

On application, the entrapped materials are then delivered to the skin in a controlled timerelease pattern
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Salient Features
The Triggers Rubbing
Perspiration

Introducing solvents
as water Elevating skin surface temperature
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How Does MS Works?

The microspheres hold the medication in reserve
Allowing the skin to absorb small amounts of active

drug over time

Microspheres themselves remain on top of the skin

Thereby reducing irritation or almost no irritation

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Conventional Vs Microsponge Technology

Conventional dosage form provide active ingredients in relatively high concentrations, with a short duration of action This may lead to a cycle of short-term overmedication followed by long-term undermedication Serious side effects can occur when active ingredients penetrate the skin in high concentration
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Contd.
Microsponge technology allows an even
medication

Sustained rate of release, maintaining long

term efficacy

Reduced or no irritation
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Conventional Vs Microsphere Technology

Parameters Conventional Microsphere

Drug medication
Duration of action Release pattern Side effects

Higher
Shorter Indefinite Rashes or Irritation
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Lower
Longer Sustained Reduced irritation & high efficacy

Patch test results

Patch test report: concluded that the
incidence of hypersensitivity and side effects like erythema, dryness and scaling is minimal with microsphere adapalene as compared to conventional formulations of adapalene available presently.
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Deriva : Competition
Indirect : Retino - A (J & J) Benzac AC (Galderma) Direct :

Adaferin (Galderma)
Adiff (IPCA)
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