semisolids intro,formulation,methods of preparation, recent advaces in semisolids ,

1. DERMATOLOGICALS

2. CONTENTS
• INTRODUCTION
• FORMULATION OF SEMISOLID DOSAGE FORM
• METHODS OF PREPARATION
• EVALUATION PARAMETERS
• RECENT ADVANCES IN SEMISOLIDS
• NOVEL ADVANCES IN SEMISOLID APPLICATION
• RECOMMENDATION AND CONCLUSION
• REFERENCE

3. INTRODUCTION
• Dermatologicals are usually semi-solid dosage forms
having a semi-solid consistency which when applied to
the skin performs therapeutic, protective or cosmetic
function.
• Semi solids comprises the group of products which
when applied to the skin or mucous membrane tend to
alleviate or treat a pathological condition or offer
protection against a harmful environment.
• They have a property to cling to the skin.
• The addition is due to the plastic rheological behavior.
• They are intended for localized drug delivery. [1]

4. Ideal properties of semi solids
• Physical properties
 Smooth texture
 Non dehydrating
 Non gritty and non greasy
 Elegant in appearance[6]
• Physiological properties
 Non irritating
 Do not alter membrane or physical properties
 Miscible with skin secretion. [6]
• Application properties
 Easily applicable with efficient drug release
 High aqueous wash ability.[6]

5. Advantage of semi-solid
dosage form:
• It can be used externally.
• Probability of side effect can be
reduced.
• Can be use for Local action.
• Firstpass gut and hepatic
metabolism is avoided.
• Patient compliance is increased,
the drug termination is
problematic cases is facilitated
as compared with other routes
of drug administration. [2]
Disadvantages of semi-solid
dosage form:
•There is no dosage accuracy in
this type of dosage form
•The base which is used in the
semi-solid dosage form can be
easily oxidized.
•Possibility of allergic reactions.
•Can be used only for drugs
which require very small plas
ma concentration for action.
•Enzyme in epidermis may
denat ure the drugs.
•Drugs of larger particle size not
easy to absorb through the skin.
[2]

6. TYPES OF CONVENTIONAL SEMISOLID DOSAGE
FORMS
• Ointments: They are semisolid preparations for external
application to skin or mucous membranes. Function as skin
protective and emollients. They are greases with the
permissible addition of up to 25% of powder by weight. [4]
• Creams: They are semisolid dosages forms that contain one
or more drug substances dissolved or dispersed in a suitable
base, usually an oil in-water emulsion or aqueous
microcrystalline dispersion of long-chain fatty acids or
alcohols that are water-washable and are cosmetically and
aesthetically acceptable. [4]
• Gels: They are semisolid systems that consist of either
suspensions of small inorganic particles or large organic
molecules interpenetrated by a liquid. Gels can be either
water based (aqueous gels) or organic solvent based
organogels. [4]
• Pastes: They are greases containing more than 25% powder
by weight are semisolid dosage forms that contain one or
more drug substances incorporated in a base with large
proportions of finely dispersed solids. They are intended for
external application to skin, but very thick and stiff. [4]

7. HUMAN SKIN
• The human skin consists of three
major layers :
a) Epidermis
b) Dermis
c) Subcutaneous tissues [1]
ROUTE OF PENETRATION
When a drug is applied topically, the drug
diffuses out of its vehicle on to the surface
tissue of the skin. There are three potential
portals of entry:
1)Through the follicular region,
2)Through the sweat ducts and
3)Through the unbroken stratum corneum
between these appendages. [1]
Fig1: Cross section of human skin Fig2: Diagrammatic representation showing
routes of penetration. [4]

8. MECHANISM OF SEMISOLIDS DRUG PENETRATION
Fig3: Absorption of semisolid dosage form through skin

9. FACTORS AFFECTING SKIN
PENETRATION
a) Physicochemical factor: Hydration of stratum corneum is one of the most important
factors that increase the penetration of the drug substance that penetrate skin.
Hydration can occur either by water diffusing from underlying epidermal layers or from
perspiration. Eg: during steroid therapy, the occlusive plastic film increase water
concentration in the stratum corneum and enhance the penetration of steroid. [1]
b) Temperature: The occlusive vehicles of semi solid drug product increase the skin
temperature by few degrees but increase skin permeability is small compare to the effect
of hydration. [1]
c) pH: According to partition hypothesis, only unionized molecule pass easily across lipid
membranes. But ionized molecules do penetrate stratum corneum to some extent as
they have great aqueous solubility than neutral species. [1]
d) Molecular size: There is little correlation between molecular size and penetration rate.
Drug having small molecular size penetrate skin more rapidly than large molecular size
drug. [1]

10. Raw
Materials
• During selection of raw materials, that materials whose chemical and
physical incompatibilities affect therapeutic efficacy of drug must be
avoided.
• Drug solubility in various materials, indicate the type of base most suitable
for the stability of the drug and for its absorption.
• Raw materials compatibility with container is very importance, and also
stability studies of the finished product must be performed. [1]
Fig4: The basic raw materials used in the development of various semisolid dosage forms. [4]

11. FORMULATION OF SEMISOLID DOSAGE FORM
• The formulation of semi solid dosage form
includes:
Bases
Antimicrobial Preservative
Humectants
Antioxidants
Emulsifier
Gelling agent
Permeation enhancer
Buffer
Perfume

12. BASES
There are four types of bases that are used to
formulate
pharmaceutical semi solids preparation:
a) Hydrocarbon bases/ oleaginous bases: These bases are anhydrous, non
washable and does not absorb water. They should not be applied to infected
skin. They are used as protectant, emollients, and vehicles
for hydrolysable drugs. Example: White Petrolatum,White Ointment.
[5]
b) Absorption bases: These bases are anhydrous substances which have
the property of absorbing (emulsifying) considerable quantity of water
but still retaining their ointment –like consistency. They are two types:
(i)Non-emulsified bases: it absorbs water and aqueous solution
producing w/o emulsion. Eg: Wool fat (ii) Water in oil emulsion: it is
capable of absorbing more water and have the properties of non-
emulsified bases. Eg: hydrous wool fat (Lanolin),Nieva [5]
c) Water removal bases: They are oil-in-water emulsions and are referred
to as cream. The vanishing cream fall into this category. The vanishing
cream are termed so because upon application and rubbing into the
skin, there is little or no visible evidence of their former presence. Due
to presence of oil-in-water emulsifier the cream get vanish from the
skin. [1]
d) Water soluble bases: They are prepared from mixture of high and low
molecular weight polyethylene glycols. Suitable combination of high
and low polyethylene glycols yields products having an ointment like
consistency, which soften and melts when applied to skin. They are
also known as greaseless ointment bases. No water is required for
their preparation. They are water soluble because of presence of many
polar groups and ether linkages.[1]

13. • ANTIMICROBIAL PRESERVATIVES: Some base, although, resist microbial attack but because
of their high water content, it require an antimicrobial preservative. Example: Methyl
hydroxyl benzoate, Propyl- hydroxybenzoate, Chlorocresol, Benzoic acid. [5]
• ANTIOXIDANTS: They are added to semisolid preparation whenever oxidative deterioration
is anticipated. Its selection depends upon the toxicity, irritancy and stability of product.
Example: Butylated hydroxy anisole, Butylated hydroxy toluene. [6]
• HUMECTANTS: They are used in semisolids to increase solubility, skin penetration of active
ingredients and to elevate the hydration of the skin. Example: Poly Ethylene Glycol, Glycerol
or Sorbitol is added as humectants. [6]
• GELLING AGENT: They forms a gel dissolves in a liquid phase as a colloid mixture that forms
a weakly cohesive internal structure. Example: Sodium alginate. [6]
• EMULSIFIER: Ideal emulsifier must reduce surface tension for proper emulsification and
have ability to increase the viscosity at low concentration. [6]
• BUFFERS: They are added to make semisolids preparation compatible with skin, for drug
stability and drug solubility.
Example: Sodium acetate. [6]

14. • PRMEATION ENHANCERS: Penetration enhancer works by reversibly
disordering the lamellar packing of stratum corneum, increasing the
thermodynamic activity of the drug and increasing the amount of drug in
solubilized form at the skin surface. Example: Limonene, Geraniol [6]
• FRAGRANCES: They are added for the patient compliance. Examples of widely
use fragrances are Lavender oil, Rose oil, Lemon oil, Almond oil [6]

15. METHODS OF PREPARATION
• There are four methods of preparation of semi solids dosage form.
1) TRITURATION METHOD:- It is commonly used method when base contains soft fats and oils,
or medicaments in insoluble or liquid. It is carried out in mortar and pestle. [5,6]
2) FUSION METHOD:- On small scale fusion method is carried out in a porcelain dish placed
over water bath. Here the ingredient of high melting point is melted then remaining
ingredient of bases are added in the decreasing order of their melting points and melted
with constant stirring. [5,6]
3) CHEMICAL REACTIONS:-In chemical reaction method a product is formed by chemical
reaction, which involves both fusion and mechanical mixing. Best example of such method is
Iodine ointment. [5,6]
4) Emulsification Method:
The four steps involve in this method are:
a) Preparation of oil and aqueous phase: The components of the oil or fat mixture are placed
into a stainless steel steam-jacketed kettle and melted. The kettle is heated to a temperature
of oil phase to prevent its components from congealing. The components of the aqueous
phase are dissolved in the purified water and also aqueous soluble drug can be added to it.
[5,6]

16. b) Mixing of the Phases: The phases are usually mixed at the temperature
of 70-720C, because at this temperature intimate mixing of the liquid
phase can occurs. The phase mixing temperature can be lowered a few
degree if the melting point of the fat phase is low enough to prevent
the premature crystallization. The phase can be mixed by three ways:
(i)Simultaneous blending of the phase (ii) Addition of discontinuous
phase to continuous phase (iii) Addition of continuous phase to
discontinuous phase. [5,6]
c) Cooling the emulsion: The rate of cooling is generally slow to allow
adequate mixing while emulsion is still liquid. The temperature of
cooling medium in kettle jacket should be decrease at a rate consistent
with the mixing of the emulsion to prevent formation of the congealed
masses of ointment or cream. The perfume must be added at a 43-
450C temperature. [5,6]
d) Homogenization: Those semi solids preparations that need further
treatment are then transfer or pumped to homogenizer, the selection
of which is governed by the degree and the rate of shear stress
required. The choice includes a low-shear pump, a roller mill, a colloid
mill and a valve type homogenizer. Uniform dispersion of an insoluble
drug in a semi solid, as well as reduction of the size of the fatty
aggregates can be achieved by the passage of the warm ointment or
cream through a homogenizer or mill. [5,6]

17. EVALUATION PARAMETERS OF SEMI SOLID DOSAGES FORM
a) Evaluation of gel [7]
– Drug content
– Measurement of pH
– Viscosity
– Spreadability
– Extrudability
b) Evaluation of ointments [7]
– Penetration
– Irritant effect
d) Evaluation of paste [7]
– Abrasiveness
– Particle size
– Cleansing property
– Consistency
e) Evaluation of cream [7]
– Sensitivity
– Biological testing
– Phase separation
– Globule size
– Rheological properties

18. RECENT ADVANCES IN SEMISOLIDS
• RECTAL OINTMENT
• CREAMS CONTAINING MICROSPHERES
• LAMELLAR FACED CREAMS
• CREAM CONTAINING LIPID NANOPARTICLES
• ORGANOGEL OF SORBITAN MONOSEARATE
• ORGANOGELATION OF LECITHIN
• AMPHIPHILIC GEL
• BIOADHESIVE GEL
• THERMOSENSITIVE SOL-GEL REVERSIBLE HYDROGEL
• COMPLEXATION GEL

19. 1) RECTAL OINTMENT:
It is used for the symptomatic relief against inflammation associated with
hemorrhoids, anal fissure and fistulas. Rectal ointment should be applied
several times in a day according to the severity of the condition. For
intrarectal use, special applicator are also available. [2]
2) CREAMS CONTAINING MICROSPHERES:
Albumin microsphere containing vitamin A can be administered by using
creams topically.
222 ± 25 μm size of microsphere of vitamin A were produced by emulsion
method.
The In-vivo study revealed that these microspheres were able to remain
on skin for long period of time, and prolong the release of vitamin A [2]
3) LAMELLAR FACED CREAMS:
They are liquid paraffin in water emulsion prepared from cetrimide / fatty
alcohol like mixed emulsifiers and ternary system formed by dispersing
the mixed emulsifier in require quantity of water.
The cationic emulsifying wax showed phenomenal swelling in water and this
swelling was due to electrostatic repulsion which can be suppressed by
addition of salt and can be reduced by changing surfactant counter ion.
[2]

20. CREAM CONTAINING LIPID NANOPARTICLES:
•Occlusion of cream is important criteria since it
increases the penetration of topical drugs. This can be
achieved by using oils and semisolid paraffin in large
quantities.
• The development of a water-in-oil cream containing
small particles of solid paraffin was studied.
•Solid paraffin nanoparticles were incorporated in the
aqueous phase of a water-in-oil cream wherein the
aqueous phase was divided into small droplets.
• Here the oil phase served as a lubricant for
nanoparticles.
• Hence cream containing nanoparticles have a high
degree of occlusivity and also prevent a rough feel during
application. [2]

21. Oraganogel of Sorbitan monostearate:
•Sorbitan monostearate is a hydrophobic nonionic surfactant, gels a number of organic
solvents such as hexadecane, isopropyl myristate, and a range of vegetable oils.
•Gelation is achieved by dissolving/dispersing the organogelator in hot solvent to produce
an organic solution/dispersion, which, on cooling sets to the gel state.
•Cooling causes a decrease in the solvent-gelator affinities, such that the surfactant
molecules self-assemble into toroidal inverse vesicles. Further cooling results in the
conversion of the toroids into rod-shaped tubules.
•Once formed, the tubules associate with others, and a three-dimensional network is formed
which immobilizes the solvent. An organogel is thus formed.
•Sorbitan monostearatre organogels has ability to solubilise poorly water soluble drugs so it
is use as delivery vehicles for drugs. [2]
Organogelation of Lecithin:
•Initially, the lecithin molecules are randomly dispersed in the organic medium.
•With the addition of small amount of water, the lecithin molecules will assemble in
spherical reverse micellar form.
•Further addition of water makes the cylindrical micellar aggregate. The water molecules
bind
to hydrophilic head of the lecithin molecules.
•A further increase in a small amount of water results in the formation of long and flexible
tubular micellar structures .
•Thousands of such tubular micro-structures overlap and entangle with each other to form a
three-dimensional gel network. Then organic liquids get entrapped in the spaces between
the entangled reverse micelles. [8]

22. Fig7: Process of Organogelation[8]

23. Amphiphilic gels:
• Amphiphilic gels can prepared by mixing the solid gelator like sorbitan
monostearate or sorbitan monopalmitate and the liquid phase like liquid sorbitan
esters or polysorbate and heating them at 60°C to form a clear isotropic sol phase,
and cooling the sol phase to form an opaque semisolid at room temperature.
•Amphiphilic gel microstructures consisted mainly of clusters of gelator molecules
tubules that had aggregated upon cooling of the sol phase, forming a 3D network
throughout the continuous phase.
• At temperatures near the skin surface temperature, the gels softened
considerably, this would allow topical application. [9]
Fig8: Amphiphilic gel structure[9]

24. BIOADHESIVE
GELS:
• Chitosan bioadhesive gel was formulated for nasal delivery of insulin.
• The gels contained 4000 Iu/dl insulin, 2 or 4% of low and medium
molecular weight of chitosan, and lecithin or EDTA. Drug release was
studied by a membraneless diffusion method and bioadhesion by a
modified tensiometry test.
• Formulations containing 2% of low molecular weight of chitosan with
EDTA had higher release percentage and bioadhesion than gels containing
4% of medium molecular weight of chitosan with lecithin.
• The gel of 2% medium molecular weight of chitosan with EDTA caused
increase in insulin absorption and reduction the glucose level by as much
as 46% of the intravenous route. [2]

25. Thermosensitive sol-gel reversible
hydrogel:
• They are the aqueous polymeric solutions which undergo reversible sol
to gel transformation under the influence of environmental conditions
like temperature and pH which results in in-situ hydrogel formation. [9]
• Advantages :
a) It is easy to mix pharmaceutical solution rather than semisolids
b) Biocompatibility with biological systems
c) Convenient to administer
d) The pharmaceutical and biomedical uses of such sol-gel
transition include solubilization of low molecular-weight
hydrophobic drugs
e) Release can be in a controlled fashion. [9]

26. Complexation gels:
-
• The goal of oral insulin delivery devices is to protect the sensitive
drug from proteolytic degradation in the stomach and upper
portion of the small intestine.
• In this work, pH-responsive hydrogels are used as oral
delivery
vehicles for insulin.
• Insulin was loaded into polymeric microspheres and administered
orally to healthy and diabetic Wistar rats.
• In the acidic environment of the stomach, the gels were unswollen
due to the formation of intermolecular polymer complexes. The
insulin remained in the gel and was protected from proteolytic
degradation.
• In the basic and neutral environments of the intestine, the
complexes dissociated which resulted in rapid gel swelling and
insulin release. [7]

27. IDEAL PROPERTIES OF NOVEL SEMISOLIDS:
a)Novel ointment bases:
i)Should absorb more water and enhance permeation.
ii)When applied over skin,an oleaginous ointment film should formed
which prevents moisture evaporation from the skin.
iii)Should not irritate skin. Substances (e.g., hydrocarbon bases) conform
an occlusive barrier on the skin that prevents.
b)Novel semisolids are safe even when applied to inflamed skin.
c)They should be odorless, easy to handle, stable and compatible with large
range of drugs and should be safe
d)Use of Novel semisolids in pediatric, geriatrics and pregnant women should
be safe without causing any allergic reaction.
e)Novel semisolids should able to extend the release pattern in a controlled
manner.
f)Novel semisolid should allow its use in different routes of administration
with safe, odorless, easy to handle and compatible with biological
membrane. [9]

28. NOVEL ADVANCES IN SEMISOLID APPLICATIONS
• Nasal route
• Nasal gels are semisolid preparations in a water soluble or water miscible vehicle
which can be use for local or systemic effect where as Nasal ointments are
prepared from either water miscible/soluble or oleaginous bases. [9]
• Uses: An example of drug that shows effectiveness upon administration as a nasal
gel, as compared to an oral tablet, is vitamin B12, where clinical studies showed a
2.5 fold increase in measurable vitamin B12 in the blood at 48 hours after
administration. [9]
• Ophthalmic:
In ocular drug delivery many physiological constraints prevent the successful drug
delivery to eye. Drug loss occur due to:
1) less capacity of cual-de-sac
2) dilution of drug due to lachrymal secretion
3) Nasolachrymal drainage
So formulation administrated by increasing the viscosity of dosage form.
Uses : Wide range of eye ointment are available for effective treatment of eye
infection. E.g. acyclovir eye ointment chloramphenicol ophthalmic ointment. [9]

29. Rectal
route
It includes ointment, cream,gel for application to perianal area.
Advantages:
•Large surface area
•By pass First pass hepatic metabolism
•Prolong residence time
•Permeability to large mol. Weight drugs such as peptide and proteins.
•Insulin gel administrated deep rectally [9]
SKIN: -
Delivery of drugs to the skin is an effective and targeted therapy for local
dermatological disorders.
Advantage :
(1)Provides a largest surface area
(2)It avoids first-pass effects, gastrointestinal irritation,
(3)And metabolic degradation associated with oral administration. [9]

30. PACKAGING OF NOVEL SEMISOLIDS
• Containers, closures and other component must not
be reactive with the semi solid preparation.
• All drug product containers and closures must be
approved by stability testing of product in the final
container in which it is marketed.
• This includes stability testing of filled
container at under
around
room temperature about 200C as well as
accelerated stability testing condition
40 - 500C. [9]

31. RECOMMENDATION
 transdermal delivery must be explored and research must be
continued.
• If topically applied semisolid could provide maximum
bioavailability then it would be the most efficient route of
drug delivery as it bypasses first pass metabolism and also
possess patient compliance .
• Use of semi solid dosage form in nasal and

32. CONCLUSION
• Hence we can conclude that great opportunities for
the development of semisolid dosage forms exist
because of the diverse class of drugs that are
proposed for topical delivery.

33. References
1) Lachman L, Lieberman H. A, Kanig J. L., Theory and Practice of Industrial Pharmacy.
4th Indian Edition. 1991, Verghese Publishing House. 534- 563.
2) Patel Pinkesh, et al , “Recent Advances in Novel Semisolid Dosage Forms: An
Overview”, Journal of Biomedical and Pharmaceutical Research 2 (1) 2013, 09-14
Page9 ISSN: 2279 - 0594 ,”
3) Debjit Bhowmik1* , Harish Gopinath1 ,“Recent Advances In Novel Topical Drug
Delivery System”, ISSN: 2277- 7695 CODEN Code: PIHNBQ ZDB-Number: 2663038-2 IC
Journal No: 7725 Vol. 1 No. 9 2012
4) Sonje A.,Thube R.,Parmar V.,Kumari G.,Deshpande P, “A review on penetration
enhancers for semi solids”, Asian journal of pharmaceutical research and
development, vol 1(5),94-107,sept-oct 2013.
5)www.authorstream.com/Presentation/6928373561-1947670-semisolid-dosage-
forms
6)www.slideshare.net/docmano15/semi-solid-dosage-forms 7)
Aditya Bora, Sambhaji Deshmukh , “Recent advances in semisolid dosage form”,
International Journal of Pharmaceutical Sciences And Research”Inclusion in Web of
Science (Thomson Reuters) – ESCI Projected Impact Factor (2015): 1.11
8)Sushil Rauta,n , Santosh Singh Bhadoriyaa et al,” Lecithin organogel: A unique
micellar system for the delivery of bioactive agents in the treatment of skin aging”,
Acta Pharmaceutica Sinica B 2012;2(1):8–15
9)Mandore Paresh; Sharma R.K.; et al, “A Review : Novel Advances in Semisolid
Dosage Forms & Patented Technology in Semisolid Dosage Forms”, International
Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol. 3, No.1, pp
420-430, Jan-Mar 2011

34. THANK
YOU….!!!!