INTRODUCTION:

The drug delivery technology landscape has become highly competitive and rapidly evolving. More and more developments in delivery systems are being integrated to optimize the efficacy and cost-effectiveness of the therapy. New classes of pharmaceuticals, biopharmaceuticals (peptides, proteins and DNA-based therapeutics) are fuelling the rapid evolution of drug delivery technology. These new drugs typically cannot be effectively delivered by conventional mean. Drug delivery systems (DDS) that can precisely control the release rates or target drugs to a specific body site have had an enormous impact on the health care system. [1, 2]

Conventional formulations of topical drugs are intended to work on the outer layers of the skin. Typically, such products release their active ingredients upon application, producing a highly concentrated layer of active ingredient that is rapidly absorbed. Moreover, the application of topical drugs has many problems like greasiness, stickiness associated with the ointments and so on, that often result in lack of patient compliance. Conventional dermatological products typically provide active ingredients in relatively high concentrations but with a short duration of action. This may lead to a cycle of short term overmedication followed by long-term under medication. Rashes or more serious side effects can occur when active ingredients penetrate the skin. It could be overcome by using a unique, versatile and novel approach Microsponge drug delivery system. Microsponge technology allows an even and sustained rate of release, reducing irritation while maintaining efficacy. The microsponge technology was developed by Won in 1987, and the original patents were assigned to Advanced Polymer Systems, Inc. [3, 4] This company developed a large number of variations of the technique and applied to the cosmetic as well as over the counter (OTC) and prescription pharmaceutical products. At present, this technology has been licensed to Cardinal Health, Inc. for use in topical products.

A microsponge delivery system (MDS) is highly cross linked, patented, porous, polymeric microspheres that acquire the flexibility to entrap a wide variety of active ingredients such as emollients, fragrances, sunscreens, essential oils, anti-infective, anti-fungal and anti-inflammatory agents etc and are used as a topical carrier system. Resembling a true sponge, each microsphere consists of an innumerable of interconnecting voids within a non-collapsible structure with a large porous surface. It is a unique technology for the controlled release of topical agents which consists of micro porous beads normally 10-25 microns in diameter, loaded with active ingredients that is subsequently releases them onto the skin over a time in a controlled manner or in response to triggers including rubbing, pH, friction, applied to the skin, the drug release can be controlled through diffusion. This controlled release of active ingredient onto skin over time is an enormously important tool for providing the benefits of enhanced product efficacy, tolerability, mildness and lessen the irritation usually associated with powerful therapeutic agents like retinoids or benzoyl peroxide and extended wear to a wide range of skin therapies. This system has been utilized for the improvement of performance of topically applied drug. MDS technology is now being presently used in cosmetics, over-the-counter (OTC) skin care, sunscreens and prescription products. [5, 6]

Defining Microsponges: -

The Microsponge Delivery System (MDS) is a patented polymeric system consisting of porous microspheres. They are tiny sponge like spherical particles that consist of a myriad of interconnecting voids within a non-collapsible structure with a large porous surface through which active ingredient are released in a controlled manner. The size of the microsponges ranges from 5-300μm in diameter and a typical 25μm sphere can have up to 250000 pores and an internal pore structure equivalent to 10 feet in length, providing a total pore volume of about 1ml/g for extensive drug retention. The surface can be varied from 20 to 500 m2/g and pore volume range from 0.1 to 0.3cm3/g. This results in a large reservoir within each microsponge, which can be loaded with up to its own weight of active agent. [7]

Figure 1: View of Microsponge.

Advantages of Microsponge Delivery System: -

· Microsponges can absorb oil up to 6 times its weight without drying.

· It provides continuous action up to 12 hours i.e. extended release.

· Improved product elegancy.

· Lessen the irritation and better tolerance leads to improved patient compliance.

· It can also improve efficacy in treatment.

· They have better thermal, physical and chemical stability.

· These are non-irritating, non-mutagenic, non-allergenic and non-toxic.

· MDS allows the incorporation of immiscible products.

· They have superior formulation flexibility.

· In contrast to other technologies like microencapsulation and liposomes, MDS has wide range of chemical stability, higher payload and are easy to formulate.

· Liquids can be converted in to powders improving material processing.

· It has flexibility to develop novel product forms.

· MDS can improve bioavailability of the drugs. [8]

Characteristics of Microsponges: -

· Microsponge formulations are stable over range of pH 1 to 11;

· Microsponge formulations are stable at the temperature up to 130oC;

· Microsponge formulations are compatible with most vehicles and ingredients;

· Microsponge formulations are self sterilizing as their average pore size is 0.25μm where bacteria cannot penetrate;

· Microsponge formulations have higher payload (50 to 60%), still free flowing and can be cost effective. [9, 10]

Methods of Preparation of Microsponges: -

1) Liquid-Liquid suspension polymerization- In this method of polymerization the monomer is dissolved along with the active ingriendts in suitable solvent and then added in aqueous phase containing additives i.e. surfactant, suspending agents etc. The polymerization is then initiated by adding catalyst or by increasing temperature or irritation. Polymerization of styrene or methyl methacrylate is carried out in round bottom flask. A solution of nonpolar drug is made in the monomer, to which aqueous phase, usually containing surfactant and dispersant to promote suspension is added. Polymerization is effected, once suspension with the discrete droplets of the desired size is established, activating the monomers either by catalysis or increased temperature. When the drug is sensitive to the polymerization conditions, two step process is used. The polymerization is performed using substitute porogen and is replaced by the functional substance under mild experimental conditions.

Fig. 1: Reaction vessel for Micropsaonge

The various steps in the preparation of microsponges are summarized as follows: -

· Selection of monomer or combination of the monomer

· Formation of chain monomer as polymerization begins

· Formation of monomer ladder as result of cross linkage between chain monomer

· Folding of monomer ladder to form spherical particles

· Agglomeration of microsphere lead to formation of bunches of microsphere Binding of bunches lead to formation of microsponge.

2) Quasi-emulsion solvent diffusion: -

To prepare the inner organic phase, Eudragit RS 100 is dissolved in ethyl alcohol. Next, the drug is added to the solution and dissolved under ultra sonication at 35°C. The inner phase is poured into the polyvinyl alcohol solution in water (outer phase). Following 60 minutes of stirring, the mixture is filtered, to separate the microsponges. The microsponges are dried in an air-heated oven at 40ºC for 12 hours. [10-15]

Fig. 2: Quasi-Emulsion Solvent Diffusion Methods

Safety Consideration: - Safety studies of microsponges can be established by:

· Eye irritation studies in rabbits.

· Skin irritation studies in rabbits.

· Mutagenicity in bacteria.

· Oral toxicity studies in rats.

· Allergenicity in guinea pigs. [16]

Drug Release Mechanism: - Microsponges can be intended to release given amount of active ingriendts over time in response to one or more following external triggers i.e. pressure, temperature change and solubility etc which are described as follows

1. Temperature change: At room temperature, few entrapped active ingredients can be too viscous to flow suddenly from microsponges onto the skin. With increase in skin temperature, flow rate is also increased and therefore release is also enhanced.

2. Pressure: Rubbing or pressure applied can release the active ingredient from microsponges onto skin.

3. Solubility: Microsponges loaded with water miscible ingredients like antiseptics and anti perspirants will release the ingredient in the presence of water. The release can also be activated by diffusion but taking into consideration, the partition coefficient of the ingredient between the microsponges and the external. [17]

Evaluation Parameters of Micro Sponges: -

1. Particle size (Microscopy):- The most widely used procedures to visualize microparticles are conventional light microscopy (LM) and scanning electron microscopy (SEM). Both can be used to determine the shape and outer structure of microparticles. LM provides a control over coating parameters in case of double walled microparticles. The microparticles structures can be visualized before and after coating and the change can be measured microscopically. SEM provides higher resolution in contrast to the LM. SEM allows investigations of the microparticles surfaces and after particles are cross-sectioned, it can also be used for the investigation of double walled systems. Conflocal fluorescence microscopy is used for the structure characterization of multiple walled microparticles. Laser light scattering and multi size coulter counter other than instrumental methods, which can be used for the characterization of size, shape and morphology of the microparticles (microsponges). [18]

2. Morphology and surface topography of microsponges:- For morphology and surface topography, prepared microsponges can be coated with gold-palladium under an argon atmosphere at room temperature and then the surface morphology of the microsponges can be studied by scanning electron microscopy (SEM). SEM of a fractured microsponge particle can also be taken to illustrate its ultra structure. [19]

Figure 4: SEM photographs of microsponge formulations at different magnification.

Recent Advances in Microsponge Drug Delivery System:-

Various advances were made by modifying the methods to form nanosponges, nanoferrosponges and porous microbeads. β-CD nanosponges were also developed that can be used for hydrophobic as well as hydrophilic drugs, in contrast to polymeric micro or nanosponges. These advanced systems were studied for oral administration of dexamethasone, flurbiprofen, doxorubicin hydrochloride, itraconazole and serum albumin as model drug. These nanosponges were developed by cross-linking the β-CD molecule by re-acting the β-CD with diphenyl carbonate. Some researchers also observed the nanosponges as good carrier for the delivery of gases. Researchers also observed that incorporating a cytotoxic in a nanosponge carrier system can increase the potency of the drug suggesting that these carriers can be potentially used for targeting the cancerous cells [30]. Nanoferrosponge, a novel approach constituted the self-performing carriers having better penetration to the targeted site due to the external magnetic trigger which enforces the carriers to penetrate to the deeper tissue and then causing the removal of magnetic material from the particle leaving a porous system [31]. Due to the improved characteristics of porous microspheres, process was developed to produce the porous micro beads. This method (High internal phase emulsion, HIPE) consisted of the monomer containing continuous oil phase, cross linking agent and aqueous internal phase [32]. They also observed an improved stability of RNA and the relatively effective encapsulation process of siRNA. The approach could lead to novel therapeutic routes for siRNA delivery. [33]

Future Prospects: -

Microsponge drug delivery system holds a promising opportunity in various pharmaceutical applications in the upcoming future as it has unique properties like enhanced product performance and elegancy, extended release, improved drug release profile, reduced irritation, improved physical, chemical and thermal stability which makes it flexible to develop novel product forms. The real challenge in future is the development of the delivery system for the oral peptide delivery by varying ratio of polymers. The use of bioerodible and biodegradable polymers for the drug delivery is enabling it for the safe delivery of the active material. As these porous systems have also been studied for the drug delivery through pulmonary route which shows that these system can show effective drug release even in the scarce of the dissolution fluid thus colon is an effective site for targeting for drug release. These carriers also require to be developed for alternative drug administration routes like parenteral and pulmonary route. These particles can also be used as the cell culture media and thus can also be employed for stem cell culture and cellular regeneration in the body. Due to their elegance, these carrier systems have also found their application in cosmetics. These developments enabled researchers to utilize them variably. These novelties in formulation also open new ways for drug deliver. [34]

CONCLUSION:

Microsponge drug delivery system is advantageous over the conventional topical drug delivery due to its properties like Ease manufacturing, simple ingredients and wide range drugs can be entrapped. MDS is originally developed for topical delivery of drugs like anti-acne, anti-inflammatory, anti-fungal, anti-dandruffs, antipruritics, rubefacients etc. Microsponge can be effectively incorporated into topical drug delivery system for retention of dosage form on skin, and also use for oral delivery of drugs using bioerodible polymers, especially for colon specific delivery and controlled release drug delivery system thus improving patient compliance by providing site specific drug delivery system and prolonging dosage intervals. It provides a wide range of formulating advantages. Liquids can be transformed into free flowing powders. Formulations can be developed with otherwise incompatible ingredients with prolonged stability without use of preservatives. Safety of the irritating and sensitizing drugs can be increased and programmed release can control the amount of drug release to the targeted site.

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Received on 04.07.2015 Accepted on 25.10.2015

Research J. Topical and Cosmetic Sci. 6(2): July-Dec. 2015 page 77-85

DOI: 10.5958/2321-5844.2015.00011.4