Submitted to:

Dr. P. Srinivasa BabuM. PHARM, PhD

G. Kishore BabuM. PHARM, (PhD)

Submitted by:

S. Lalitha Sravani

M. Pharmacy (I/II)

Pharmaceutics

10AB1S0306

RECENT ADVANCES IN FORMULATION OF SEMISOLIDS

• Pharmaceutical semisolid preparations may be defined as topical products intended for application on skin or accessible mucous membrane to provide localized and some times systemic effect at the site of application.

• The adhesion is brought about by plastic rheological behavior that allows that allows the semisolids to retain shape and cling as film until acted on by an outside force where upon they deform and flow.

TYPES OF SEMISOLIDS

OINTMENTS

• Semisolid preparations for external application to skin or mucous

membranes.• Their composition softens but does not melt upon application to the skin.• Primarily, ointments function as skin protective and emollients.• Therapeutically as vehicles for the topical application of drug substances.

CLASSIFICATION OF OINTMENTS : Based on penetration through skin.

1. Epidermic ointments : protectives, antiseptics.

2. Endodermic ointments : emollient, local irritant.

3. Diadermic ointments : systemic effect.

CREAMS

• These are semisolid emulsions (o/w). • Softer consistency and lighter than ointments.

• Uses water soluble bases so they are less greasy, easy to apply and remove.

• CLASSIFICATION : Based on type of bases used in the preparation

• Aqueous creams :

• Anionic emulsifying creams : sodium lauryl sulphate.

• Cationic emulsifying creams : cetrimide, benzalkonium chloride

• Oily creams:

• Sterol creams : wool fat, wool alcohol.

• Soap creams : calcium soap, borax soap.

• Triethanol amine creams: oleic and stearic acid

PASTES

semisolid dosage forms that contain one or more drug substances

incorporated in a base with large proportions of finely dispersed solids, are

intended for external application to skin, but very thick & stiff.

• protective action pastes absorb serious discharges from

skin lesions.• therapeutic action ointments and creams.

CLASSIFICATON OF PASTES :

1. Fatty pastes : Zon paste.

2. Non-Greasy pastes : Bassorin paste.

GELS

• semisolid systems consisting of condensed mass enclosing and interpenetrated by a liquid.

• Gels are aqueous colloidal suspensions of the hydrated forms of insoluble medicament.

• When the coherent mass is richer in liquid, the product is called jelly.• Jellies are transparent or translucent non-greasy semisolid gels.

• When the liquid is removed and only frame work remains the gel is known as xerogel.

• Gelatin sheets, tragacanth ribbons, acacia tears.

GELLING AGENTS

PROTEINS• Collagen • Gelatin

POLYSACHARIDES• Alginates• Carrageenan• Hyaluronic acid• Pectins• Starch

SEMISYNTHETIC POLYMERS (CELLULOSE DERIVATIVES)• HPMC• Hydroxy propyl cellulose• Methyl cellulose

SYNTHETIC POLYMERS• Carbomers• Polaxomers• Polyacryl amide• Polyvinyl alcohol

INORGANIC SUSTANCES• Aluminium hydroxide• Smectite clays

TRANSITIONAL PROPERTIES OF GELS• Syneresis

• Swelling

• Imbibition

IDEAL PROPERTIES OF SEMISOLIDS

• PHYSICAL PROPERTIES.

• PHYSIOLOGICAL PROPERTIES.

• APPLICATION PROPERTIES.

• STORAGE PROPERTIES .

• HYDROPHILIC PROPERTIES.

RHEOLOGICAL PROPERTIES

FORMULATION COMPONENTS

CLASSIFICATION OF SEMISOLID BASES

PROPERTIES OF SEMISOLID BASES

METHOD OF PREPERATION

INCORPORATION METHOD :Size reduction ( #85 )

Levigation

Mixing with baseSolution of soluble drug

spatulation trituration

Mixing of base to final weight

Filling

FUSION METHOD :Grate the waxy base

Melt all the ingredients in order of M.P

cool the ingredients by stirring

Soft mass at 40°

homogenization Filling

Add heat sensitive

ingredients

EMULSIFICATION METHOD

Oil soluble ingredients

Aqueous soluble ingredients

Both are heated separately to 70○

Aqueous phase is added to oil

phase

homogenization

Filling

CHEMICAL REACTION METHOD

bases are melted

Cooled to 40○Solution of

KI complexes

PackingI2 dissolved in KI solution

MACHINES USED IN MANUFACTURING

• SIZE REDUCTION APPARATUS

1.   Mortar and pestle2.   Hammer mill 3.   Ball mill 4.   Colloid mill

MIXING EQUIPMENTS

1.   Agitator Mixers: sigma mixers and planetary2.   Shear Mixers: triple roller mill and colloidal mill 

CENTRIFUGATION APPARATUS 

1. Conical disc centrifuge or De Laval clarifier2. Super centrifuge

NOVEL ADVANCES IN SEMISOLID DOSAGE FORMS

IDEAL PROPERTIES OF NOVEL SEMI SOLIDS :

• Novel ointment bases should absorb more water and enhance permeation.

• These should form an oleaginous ointment film when applied over the skin to prevent evaporation of moisture from the skin.

• Novel semisolids do not irritate and are safe when applied to inflamed skin.

• They should be odorless, easy to handle, stable, safe and compatible with large range of drugs.

• Novel semisolids are non greasy as they are made up of water washable bases.

• They should be able to extend the release pattern in controlled manner.• They should allow its use in different routes of administration.

• Use in pediatric, geriatric and pregnant woman should be safe without any allergic reaction.

ADVANCES IN FORMULATION OF SEMISOLIDS BY CHEMICAL MEANS

CREAMS CONTAINING MICROSPHERES : albumin micro spheres (225 ± 25 µm)

Vitamin AEmulsion method

Prolonged release

LAMELLAR FACED CREAMS :

Liquid paraffin in water emulsions

cetrimide

Swelling in water

CREAM CONTAINING LIPID NANO PATICLES :

Water in oil creams where aqueous phase divided into small droplets

Nanoparticles incorporated in the aqueous phase

Smooth cream

ORGANOGELS :

Organo gelators immobilize large volume of organic solvents followed by their self assembly into 3D network.

These gels are thermoreversible and affected by the presence of hydrophilic surfactant, polysorbate.

Sorbitan stearate and palmitate have potential application as delivery vehicles for drugs and antigens.

BIOADHESIVE GELS :

AMPHIPHILIC GELS :

Solid gelator Liquid phase

Clear isotropic sol phase60°

Cooling

Gel structure

• Sorbitan monostearate.• Sorbitan

monopalmitate.

• Liquid sorbitan esters• polysorbates

Chitosan bioadhesive gel was formulated for nasal delivery of insulin.

Drug release was studied by a membrane less diffusion method and bioadhesion by a modified tensiometry test.

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.

LIPOSOMES AS DRUG CARRIERS : • Liposomes are microscopic vesicles composed of membrane-like lipid layers

surrounding an aqueous compartment.• They also serve as reservoir for the prolonged release of drugs within various

skin layers

HYDROGELS : • Bicoherent systems.• Internal phase hydrophilic polymer coherent 3D network.• External phase liquid vehicle• Intermolecular forces bind solvent molecules to polymeric net structured

systems

NON AQUEOUS GELS :• Ethyl cellulose propylene glycol dicaprylate • Prominent viscoelastic behavior, yield stress and thixotropy.• Solvent molecular conformations play a role in affecting the formation of gel

matix.

.

VOLATILE VEHICLE-ANTINUCLEANT POLYMER SYSTEMS :

• Increasing the thermodynamic activity of drug molecules was found to be the most efficient approach.

• In supersaturated solutions the drug is in a high state of activity and has a great leaving tendency, resulting in increased flux.

OLEO HYDRO GEL SYSTEMS :

Ketoprofen Emulsion of oil and carbomer hydrogel

N-methylpyrrolidoneBetter bio availability

THERMOSENSITIVE GELS :

Aqueous polymeric solutions which undergo reversible sol to gel transformation under the influence of environmental conditions.

pH SENSITIVE GELS : • Facilitates oral insulin delivery by complexing with pH responsive poly

methacrylic ethylene glycol hydrogels.

ADVANCES IN FORMULATION BY BIOLOGICAL MEANS

NOVEL APPROACHES OF SEMISOLID DOSAGE FORMS BY PHYSICAL MEANS

• IONTOPHORESIS:

It is the process of applying electric current to increase penetration of electrically charged drugs through the surface tissue.

• ELECTROPHORESIS :

The cells exposed to high intensity electric field pulses (up to several 100 volts for milliseconds) become highly permeable to exogenous compounds in the surrounding media.

• SONOPHORESIS :

It is defined as movement of drug through intact skin and underlying soft tissues by the influence of ultrasonic perturbation.

APPLICATIONS OF NOVEL SEMISOLIDS

NASAL ADMINISTRATION :

• Intranasal vitamin B-12 gel Nascobal produced by Schwarz Pharma• Used as dietary supplement.

• Phenylephrine hydrochloride neo-Synephrine viscous by Sanofi • Used as nasal decongestant Winthrop

OCCULAR DELIVERY SYSTEMS

POLYMERS USED FOR EXTENDED RELEASE OF OCCULAR SEMISOLIDS

MARKETED PRODUCTS

PARENTRAL ADMINISTRATION USING ATRIGEL TECHNOLOGY

ADVANTAGES• Compatibility with broad range of

pharmaceutical compounds.

• Direct delivery to targeted area.

• Less invasive technique.

• Protection of drug.

• Sustained drug release.

• Bio-degradable and Biocompatible.

• Economical.

ATRIGEL DRUG DELIVERY FORMULATION

WATER INSOLUBLE BIO-DEGRADABLE POLYMER

BIO-COMPATIBLE SOLVENT

DRUG

SUSPENSION

OF DRUG

Polymer matrix solidifies on contact with aqueous body fluids in to which the drug becomes entrapped

• Polyhydroxyacids• Polyanhydrides.• Polyorthoesters.• Polyesteramides.

HYDROPHYLIC SOLVENTS

• Dimethyl sulphoxide.• N-methhyl-2-pyrollidone.• Tetra glycol.• Glycol furol.

HYDROPHOBIC SOLVENTS

• Propylene carbonate.• Triacetin.• Ethyl acetate.• Benzyl benzoate.

BIODEGRADABLE POLYMERS:

BIOCOMPATIBLE SOLVENTS:

MARKETED PRODUCTS BASED ON ATRIGEL TECHNOLOGY

VAGINAL DELIVERY SYSTEMS

RECTAL DELIVERY SYSTEMS

NAME COMPANY API DOSGE FORM

USE

ANUSOL GlaxoSmithKline Starch Ointment hemorrhoids

TRONOLANE Ross Pramoxine Hcl

Cream Analgesic Antipruritic

NAME COMPANY API DOSAGEFORM

USE

TERAZOL-7 OrthoMcNeil Terconazole Cream Antifungal

PREMARIN Wyeth-agerst Conjugate estrogen

Cream Vaginitis

PATENTED TECHNOLOGIES IN SEMISOLIDS

• Delivery of monoclonal antibodies using semisolid dosage forms.

• Topical delivery of vitamin A.

• Delivery of epidermal growth factors by topical route.

• Topical medication for orofacial neuropathic pain.

• Foam drug delivery.

EVALUATION OF SEMISOLIDS

IN PROCESS CONTROL : PH Viscosity. Uniformity of distribution of active ingredient. Physical appearance and stability. Measurement of density or specific gravity.

MICROBIAL TEST : Ophthalmic preparations need to be sterile. Dermatological products should be examined for pseudomonas aeruginosa

and staphylococcus auerus.

TEXTURE ANALYSIS : Ointment flow characteristics. Gel strength measurement. Tube extrusion force.

IN VITRO RELEASE STUDY

Higuchi diffusion equation:

Q =[ D(2A-CS)CS t]1/2

Q = amount of drug released at time T per unit area of exposure.

Cs= solubility of drug in mass per cm3 in the ointment.

A = total conc. Both dissolved and undissolved.

D = diffusion coefficient of drug in ointment (cm2/sec).

Plexiglas flow through cell. Franz diffusion cell.

INSTRUMENTAL ANALYSIS UV Spectrophotometer. FT-NIR transmission spectroscopy. USP type 2 dissolution apparatus.

IN VIVO DRUG RELEASE STUDY

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