BPH 1073 DOSAGE FORM

DESIGN AND
DISPENSING II

NOVEL ADVANCES IN
SEMI-SOLID DOSAGE
FORMS:
OINTMENT, CREAM, AND GEL

SITI AMIRAH HAKIMAH BINTI MOHD

FAIRUZ
BPH COHORT 7
2062181008
S.POONGUZHALI
A
1 OINTMENT

A. FORMULATION AND EVALUATION OF NOVEL COMBINED HALOBETASOL

PROPIONATE AND FUSIDIC ACID OINTMENT

Introduction:
Combination of Halobetasol propionate and Fusidic acid is good rational and
novel for the treatment of Atopic Dermatitis, where inflammations reduce by
Halobetasol propionate and secondary bacterial infection treated with Fusidic
acid.

Type of Formulation:
Combination of Halovetasol propionate and Fusidic acid in water miscible base.

Purpose-Indications/Uses:
This type of ointment is used for eczematous diseases like Atopic Dermatitis.
Atopic Dermatitis is a chronic, relapsing noncontiguous disease and highly
purities condition and children are more prone to the disease and a significant
number of affected children continue to experience symptoms in their adulthood.
It can be prevent by administration of drugs through topical route having the
ability to deliver a higher concentration of drug to the skin than would be possible
with systemic therapy.
Important treatment goals include providing moisture to the skin, preventing
dryness and avoiding purities. As a result, the occurrence of inflammation should
concomitantly decline. Thus, a combination in topical treatment with antibacterial
and corticosteroid agent has been recommended.

Method of Preparation:
From the results, it is clearly evident that all formulations showed good
extrudability, homogeneity and spreadability. Halobetasol propionate and Fusidic
acid ointment formulation containing water miscible base showed better in-vitro
release profile and larger zone of inhibition comparison to oleaginous base. All
the formulations were drug release in between 90 % to 97 % of both Halobetasol
propionate and Fusidic acid up to the end of 5 hrs. Significant drugs release
observed and larger zone of inhibition observed in formulation in comparison to
other formulation.

Throughout several test in the study to possess optimal mechanical properties

such as ease of removal from the container, spreadability on the substrate,
rheological properties such as viscosity, elasticity, thixotropy, flowability, and
other desired property such as bioadhesion, desired drug release and absorption
were achieved greatly by the formulations of the combination of Halobetasol
propionate and Fusidic acid in water miscible base compare to oleaginous base.
 Result-Advantages:
This treatment approaches are effective and do not produce any undesirable side
effects and inhibit combination therapy. The composition of the ointment in water
miscible base are shown to be better than other formulation as it is have better
in-vitro release profile and larger zone of inhibition comparison to oleaginous
base. It also showed a good extrudability, homogeneity and spreadability. Other
than that, the combination therapy has good range of drug content of Halovetasol
propionate and Fusidic acid between 102.18% to 108.0% and 99.76% to 107.2%
respectively.

2 CREAM
A. NOVEL APPROACHES IN TREATMENT OF ACNE VULGARIS: PATENTS
RELATED TO MICROPARTICULATED CARRIER SYSTEMS

Introduction:
The available conventional formulations often cause side effects such as skin
irritation, dryness, peeling, itching, leading to reduced patient compliance and
compromised therapeutical efficacy. Novel drug delivery systems are promising
option for improved acne treatment outcome, as they can diminish the side
effects caused by the therapeutic agents or can modulate their properties and at
the same time offering possibilities for modified release and improved skin
penetration of the active substances. The cosmetics manufacturers implement
microtechnology in their formulations, while patent protection for cosmetics has
gained more importance over the past decades.

Type of Carrier System:

Microsponges.

Type of Formulation:
Different active substances used in acne treatment such as retinoids, antibiotics
and/or keratolytic agents can be combined in topical anti-acne preparation where
microsponges with benzoyl peroxide as keratolytic agent were included in the
formulation.

Combining benzoyl peroxide with other active substances in a single

pharmaceutical dosage form is oftentimes difficult since benzoyl peroxide is a
highly oxidative agent. Thus, in the present invention, its encapsulation in
microsponges prevents its reaction with the retinoids and the antibiotic.

Commonly used topical acne therapies include benzoyl peroxide, salicylic acid,
antibiotics, retinoids, azelaic acid, sulfone agents and their combinations.
Systemic antibiotics are indicated for use in moderate to severe inflammatory
acne and should be used in combination with a topical retinoid and benzoyl
peroxide.

Purpose-Indications/Uses:
 It is used for treating moderate to severe acne vulgaris (acne) in the form of
cream comprising retinoid (tazarotene or adapalene), antibiotic (clindamycin
phosphate) and/or keratolytic (2-5% of benzoyl peroxide in microsponges) which
enables a combined therapy offering fewer local side-effects. It is chronic
inflammatory dermatosis which affects the pilosebaceous unit, with a varied
clinical picture including inflammatory and non-inflammatory cutaneous lessions.
This multifactorial disease mostly occurs in adolescents; however, it can also
affect children and adults. Different therapy options for acne treatment exist,
comprising topical, systemic and hormonal agents or a combination thereof. The
choice of the therapy depends on various factors, for instance the severity and
extent of the disease and site of involvement.

Method of Preparation:
Microsponges are highly cross-linked, porous, polymeric particles which can
incorporate a large number of various active components. Commonly, these
systems are made of synthetic polymers and characterized with high degree of
cross-linking, thus resulting with particles that are insoluble and stable . The
selection of polymers, the method of preparation and the process parameters
greatly affect the size and porosity of the microsponges.

Result-Advantages:
Microsponges are interesting due to their stability over a wide pH range and high
temperatures, excellent compatibility with a large number of active ingredients
and surfaces, as well as high percentage of encapsulation of the active
ingredients. Also, in accordance with the system design, in terms of particle size
and size of pores, it is possible to achieve a predictable, controlled release. This
property of theirs is especially significant for diminishing the local side-effects
upon topical administration of the active ingredients being used in acne
treatment.

Other advantages that the microsponges offer in topical delivery are as follows:
improved physical stability and better protection from environmental factors,
sustained release of active agent thus prolonging the drug activity, ease of
incorporation into a formulated product such as cream improved elegance and
aesthetic appeal and reduction of systemic absorption of the topical agents. They
do not penetrate into the skin layers, but are retained on the surface and enable
continuous release of the active ingredient. The potential of the microsponges as
carriers of active ingredients in acne treatment has been investigated through
encapsulation of benzoyl peroxide, erythromycin, tretinoin and other active
substances. Results have shown that these carriers provide continuous release
of the drug with a concomitant decrease of the skin irritation, which are significant
benefits for achievement of effective treatment.

3 GEL
A. RECENT ADVANCES IN TOPICAL GEL FORMULATION

Introduction:
Topical gel is a localized drug delivery system, intended for administration into
eye, rectum, vagina or skin. A gel is a solid, jelly-like material that can have
properties ranging from soft and weak to hard and tough. Gels are semisolid
formulations, which have an external solvent phase, may be hydrophobic or
hydrophilic in nature, and are immobilized within the spaces of a three-
dimensional network structure.

Type of Novel Delivery System:

Emulgel. It is a combination of gels and emulsions.

Purpose-Indications/Uses:
Emulgel has emerged as promising drug delivery system for the delivery of
hydrophobic drugs. Polymer can function as emulsifiers and thickeners because
the gelling capacity of these compounds allows the formulation of stable
emulsions and creams by decreasing surface and interfacial tension and at the
same time increasing the viscosity of the aqueous phase. In fact, the presence of
a gelling agent in the water phase converts a classical emulsion into an emulgel.

These emulgel are having major advantages on novel vesicular systems as well
as on conventional systems in various aspects. In fact, a gelling agent present in
the water phase converts a classical emulsion into an emulgel. Both o/w and w/o
emulsions are used as vehicles for the delivery of various drugs to the skin.

Method of Preparation:
The gel requires an aqueous material such as water and alcohol which forms the
aqueous phase of the emulsion. Other than that, oils, emulsifiers, gelling agent
and permeation enhancers are require too.

Emulgel are prepared of the presence of gelling agent in the water phase
converts a classical emulsion into an emulgel. Both o/w and w/o emulsions are
used as vehicles to deliver various drugs to the skin. Emulsion itself is a
controlled release system where entrapped drug particles in internal phase pass
through external phase to the skin and slowly get absorbed. Internal phases act
as reservoir of drug and slowly release drug in controlled way through the
external phase to the skin. Gel forms cross linked network where it captures
small drug particles and provides its releases in a controlled manner.

Result-Advantages:
 Emulgels for dermatological use have several favorable properties such as being
thixotropic, greaseless, easily spreadable, easily removable, emollient, non-
staining, long shelf life, bio-friendly, transparent & pleasing appearance.

Besides that, these are the advantages of using emulgel:

 Delivery of hydrophobic drugs

 Low preparation cost
 Better stability & better loading capacity
 Emulgels used to prolong drugs effect having short half life
 Self-medication possible
 No intensive sonication is needed
 Avoidance of first pass metabolism
 Site specific drug delivery
 Improve patient compliance

Examples of emulgel:

Drug Category Gelling agent

Miconazole Nitrate Antifungal Carbopol
Secnidazole Antibacterial Gellan gum
Ketoconazole Antifungal Carbopol 934 &Carbopol 940
Ciprofloxacin Antibacterial Poloxamer
Ibuprofen NSAID Carbopol 940
Dimenhydrinate Antihistamine Gellan gum

4 REFERENCES

Abitha M H, Flowerlet Mathew. Recent Advances in Topical Gel Formulation. World

J. Clin. Pharmacol. Microbiol.Toxicol. Vol 1 [3] September 2015. 01-13.
Chakole, C. M., Shende, M. A., & Khadatkar, S. N. (2009). Formulation and
evaluation of novel combined halobetasol propionate and fusidic acid ointment. Int.
J. Chem. Tech. Res, 1(1), 103-116.

Sibinovska, N., Komoni, V., Netkovska, K. A., Vranic, E., Crcarevska, M. S., &
Dodov, M. G. Novel approaches in treatment of Acne vulgaris: Patents related to
micro/nanoparticulated carrier systems. Македонско фармацевтско друштво, ул.
Маршал Тито 13б/8, Скопје, Македонија Macedonian Pharmaceutical
Association, Marshal Tito 13b/8, Skopje Macedonia, 3.