Pharmaceutical Gels - Introduction

By: Pharma Tips | Views: 18016 | Date: 24-Apr-2014

A gel is a solid or semisolid system of at least two constituents, consisting of a condensed mass enclosing and interpenetrated by a liquid.

Pharmaceutical Gels - Introduction

A gel is a solid or semisolid system of at least two constituents, consisting of a condensed mass enclosing and interpenetrated by a liquid.

•    Gels are used to achieve optimal cutaneous and percutaneous drug delivery.
•    They can avoid gastrointestinal drug absorption difficulties caused by gastrointestinal pH.
•    Gels are having property to avoid enzymatic activity and drug interaction with food and drinks.
•    They can substitute for oral administration of medication when the route is unsuitable.
•    They can avoid the first pass effect, that is, the initial pass of drug substance through the human body.
•    They avoid systemic and portal circulation following gastrointestinal absorption.
•    Gels are not deactivated by liver enzymes because the liver is bypassed.
•    They are non-invasive and have patient compliance.
•    They are applied over skin for slow and prolonged absorption.
•    Gels have also been applied in pharmacy to some viscous suspension for oral use for example Aluminum hydroxide gel.
•    They have localized effect with minimum side effects.

•    Gels have possibility of allergenic reactions.
•    Enzyme in epidermis may denature the drugs of gels.
•    Drugs of larger particle size do not absorb through the skin.
•    They have poor permeability of some drugs through the skin.
•    Selection of area to be examined carefully during application of gels.
•    Gels which are used for the introduction into body cavity or the eyes should be sterilized.
•    They may cause application side reactions.
•    They may cause skin allergy during application.

Delivery of drugs to the skin is an effective and targeted therapy for local dermatological disorders. Topical gel formulations provide a suitable delivery system for drugs because they are less greasy and can be easily removed from the skin10.
Fig: Longitudinal section showing layers of skin
Advantages of This Route:
•    It provides a largest surface area.
•    It avoids first-pass effects, gastrointestinal irritation.
•    It avoids metabolic degradation associated with oral administration.

Mechanism of Drug Absorption:
The principal mechanisms of drug absorption are:
1.Passive diffusion
2.Pore transport
3.Facilitated diffusion
4.Active transport
5.Ionic or electrochemical diffusion
6.Ion-pair transport

Physiological Factors Affecting Skin Penetration13,21:
1. Skin integrity
2. Skin hydration
3. Skin temperature
4. Regional variation
5. Traumatic/pathologic injury to skin
6. Cutaneous drug metabolism

Formulation Factors Affecting Skin Penetration13,21,22:
1. Penetration enhancer.
2. Occlusivity
3. Drug concentration
4. pH
5. Solubility
6. Surfactant

Classification of Gels is Following:
A. Controlled release gels
B. Organogels
C. Extended release gels
D. Amphiphilic gels
E. Hydrophilic gels
F. Non aqueous gels
G. Bioadhesive gels
H. Thermosensitive sol-gel reversible hydrogels
I. Complexation gels
J. Hydrogel

A. Controlled Release Gels :
Drug delivery to nasal or ocular mucosa for either local or systemic action suffers from many obstacles. Gel formulations with suitable rheological and mucoadhesive properties increase the contact time at the site of absorption. However, drug release from the gel must be sustained if benefits are to be gained from the prolonged contact time.
These gels were formed in simulated tear fluid at concentrations of polymer as low as 0.1%, and it was shown that sodium was the most important gel-promoting ion in vivo. Rheology, although it may be a questionable technique for evaluating mucoadhesive properties of polymers, showed that interactions between mucin and polymers were most likely to be seen with weak gels.

B. Organogels :
Sorbitan monostearate, a hydrophobic nonionic surfactant, and numbers of organic solvents such as hexadecane, isopropyl myristate, and a range of vegetable oils are present. 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.
Such organogels are affected by the presence of additives such as the hydrophilic surfactant, polysorbate 20, which improves gel stability and alters the gel microstructure from a network of individual tubules to star-shaped "clusters" of tubules in the liquid continuous phase. Another solid monoester in the sorbitan ester family, sorbitan monopalmitate, also gels organic solvents to give opaque, thermoreversible semisolids. Like sorbitan monostearate gels, the microstructure of the palmitate gels comprises an interconnected network of rod like tubules.

C. Extended Release Gels:
It is a controlled release technology consists of an agglomerated, hydrophilic complex that, when compressed, forms a controlled-release matrix. It consisting of xanthan and locust bean gums (two polysaccharides) combined with dextrose surrounds a drug core. In the presence of water, interactions between the matrix components form a tight gel while the inner core remains unwetted.
The drug is encapsulated in the pores of the gel, and as the matrix travels through the patient’s digestive system, the tablet swells and begins to erode. This erosion allows the drug to “back-diffuse” out through the gel-matrix at a controlled rate until the matrix erodes and a majority of the drug is released. The fundamental component controlling the rate of release lies in the properties of the gel matrix.

D. 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 tubules of gelator molecules that had aggregated upon cooling of the sol phase, forming a 3D network throughout the continuous phase. The gels demonstrated thermoreversibility. Gelation temperature and viscosity increased with increasing gelator concentration, indicating a more robust gel network. At temperatures near the skin surface temperature, the gels softened considerably, this would allow topical application.

E. Hydrophilic Gels :
Hydrophilic gels are composed of the internal phase made of a polymer producing a coherent three-dimensional net-like structure, which fixes the liquid vehicle as the external phase. Intermolecular forces bind the molecules of the solvent to a polymeric net, thus decreasing the mobility of these molecules and producing a structured system with increased viscosity.

F. Non Aqueous Gels :
Ethylcellulose was successfully formulated as a nonaqueous gel with propylene glycol dicaprylate/dicaprate. The novel nonaqueous gel exhibited rheological profiles corresponding to a physically cross-linked three dimensional gel network, with suitable mechanical characteristics for use as a vehicle for topical drug delivery. Molecular conformation of the solvent was found to influence the molecular interactions associated with formation of ethylcellulose gel networks.
The gel matrices exhibited prominent viscoelastic behavior, yield stress and thixotropy. Rheological and mechanical properties showed significant upward trends with increased polymeric chain length and polymer concentrations. Good linear correlations were obtained between rheological and mechanical properties. The solvent molecular conformation was found to play a role in affecting the formation of gel networks via intermolecular hydrogen bonding between ethylcellulose polymer chains.

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