Microsponge: A Novel Tool for Topical Drug Delivery of Anti Rheumatoid Drugs

Microsponge is developing field of technology which can achieve goal of site specific as well as controlled drug delivery. Physicochemical properties of microsponge like Particle size, particle size distribution, porosity, surface morphology plays a major role in selection of type of dosage form and route of administration for delivery of drug. Microsponge is also emerged as novel tool for delivering of drug by topical route. Topical route is having added advantage of formulation flexibility, greater patient compliance, improved safety and efficacy of formulation and aesthetic properties. Rheumatoid Arthritis is immunomodulatory disease which requires long term treatment for management of disease. Available oral formulation may cause liver toxicity upon long term use. Topical route can be suitable alternate route for delivery of drug with enhanced stability of drug, reduced side effects, and reduced frequency of administration. Due to porous and spongy structure of Microsponge, it has the capacity to entrap large amount of dose and can modify drug release too.


INTRODUCTION
Arthritis is an immunomodulatory disease that mainly causes inflammation of the joints which can affect a single or multiple joints. It affects mainly geriatric patient but sometimes also observed in young age children. Further, it develops mainly in female patient compared to that of male patient [1,2].
Currently used DMARDS; Methotrexate, Leflunomide, Hydroxychloroquine, Sulphasalazine etc. are available as oral dosage forms. Long term administration of Oral formulation of drugs causes liver toxicity. Topical drug delivery system can be used as alternative route. Varieties of formulations can be used to deliver the drug for topical application [11][12][13]. Some commonly used topical formulations are cream, ointment, lotion, gel, emulgel, organogel etc. Gel is most convenient dosage form to be used topically as it contains aqueous based vehicle, highly compatible with skin, with greater rate of permeability through skin [14][15][16].
Microsponges are porous, spherical microsphere, capable of encapsulating high drug content. Due to large porous surface, it is capable to release drug for a longer period of time, in a controlled manner [17][18][19]. It is also stable for a wide range of pH and temperature [20]. Microsponges are also compatible with low dose of drug and also capable for uniform distribution of drug with a minimal dose and thereby also affects release rate of drug [21]. Microsponge can be used as a carrier for local as well as systemic drug delivery. Both hydrophilic and lipophilic drug can be incorporated and delivered through chosen route of administration. Research work for microsponge has been reported for sustained drug delivery, solubility enhancement, gastroretentive drug delivery, for topical drug delivery [22][23][24][25]. Few marketed preparations are also available for topical delivery of drug like cream, lotion, gel, powder etc. Microsponge provides a wide range of formulation flexibility depending on physicochemical characteristics of the drug [26][27][28].
Most of the drugs available are poorly water soluble causing difficulty in development of dosage forms. To enhance water solubility of drug, solubility enhancement approaches can be used. Microsponge based topical drug delivery also offers additional advantage of localized and site specific drug delivery. It also bypasses first pass hepatic metabolism as well as side effects upon oral administration of drug [29][30][31][32]. Advantages [20]  Extended release  Improved product elegancy  Flexibility to develop novel products forms  Improved oil control as it absorbs oil up to 6 times its weight without drying  Enhanced product performance  Improved formulation flexibility  Microsponge system are non-irritating, non ,mutagenic, non-allergic  Improved thermal, physical and chemical stability Disadvantages  Require long time to the reaction  No confirm uniform structure  Require vigorous washing to remove organic solvents  Probable entrapment of unreacted solvent traces  Require reflux condition  Reproducibility is less  Process condition like change in temperature, solvent addition and evaporation may  influence the stability of core material  May lead to cracking or shrinkage Characteristics of microsponge drug delivery system [20]  Microsponges show acceptable stability over pH ranging from 1 to 11 and at high temperatures  Microsponges have high entrapment efficiency up to 50 to 60%  The average pore size of micro sponges in small in a way to prevent the penetration of bacteria, thus they do not need sterilization or addition of preservatives  Microsponges absorb oil up to 6 times their weight without drying  Microsponges exhibits good compatibility with various vehicles and ingredients  Microsponges possess free flowing properties  Microsponges are non-allergenic, onirritating, non-mutagenic and non-toxic

Liquid -Liquid Suspension Polymerization Technique
In this method, monomers and other excipients are dissolved in a solvent. Solvent is selected in such a way that it is immiscible with external phase i.e. water. Solution containing monomer is than allowed to disperse in external aqueous medium containing surfactant. Dispersion of immiscible phase in aqueous phase results in formation of suspension with fine droplets. Polymerization of monomer present in suspension is promoted by catalyst, temperature or radiation (Fig. 2). Polymerization continues till the process completely utilizes monomer. Upon evaporation of solvent; porous, spongy Microsponge precipitates out which are required to be washed to remove impurity. Further, microsponges are separated from reaction media and subjected for drying [20,33,34].

Quasi-emulsion Solvent Diffusion
Microsponges can also be prepared using quasi emulsion solvent diffusion method. This method involves preparation internal organic phase and external aqueous phase. Inner phase can be prepared by dissolving polymer and drug simultaneously in common organic solvent with specified condition of stirring and temperature. Outer phase is prepared by dissolving surfactant in aqueous phase. Dropwise addition of internal phase to external phase results in formation of fine droplets dispersed in external phase. Complete evaporation of Organic solvent yield formation of tiny, porous Microsponge (Fig. 3). Isolated microsponges are then subjected to washing and subsequent drying [35][36][37].
In both discussed method of preparation, drug can be incorporated at the time of preparation if it can withstand supposed experimental condition. In case, if drug is thermolabile in nature, microsponges are pre-formed without drug. Drug is incorporated by soaking miacrosponges in saturated solution of drug for 24-48 hrs.

FTIR Spectrum
Fourier Transform Infrared Spectrophotometer is used to study drug-excipients compatibility. Previously dried drug and excipients are subjected to Spectrophotometer and spectrum is recorded in wavelength range 4000-400 cm -1 . Recorded spectrum is subjected to analysis for compatibility. Each drug and excipients are having identical spectrum due to the presence of identical functional groups and intermolecular forces involved between the molecules. Standard spectrum can be verified with test and difference can be identified [38,39].

Differential Scanning Calorimetry (DSC)
DSC is performed to study thermal behaviour of drug, polymer and other excipients. DSC is also used to check compatibility between drug and excipients. Study is carried out by compressing dry solid sample between two aluminium pans. Further, it is subjected to gradual heating with constant purging of nitrogen flow rate. Thermogram obtained using this procedure is studied for accessing amorphous or crystalline nature of components to be studied [40,41].

Microscopic Analysis
Optical microscopy can be carried out by using lab scale microscope. Slide can be prepared by Sprinkling a thin layer of dried Microsponge and observed under Optical microscope using standard magnification. Particle size and Particle size analysis can also be performed. Further, optical microscope can be connected with camera to capture the photograph of prepared Microsponge [42,43].

Scanning Electron Microscopy (SEM)
Scanning electron microscopy is performed to study three dimensional surface morphology of prepared microsponge. SEM uses a probe which can scan only conductive material. Hence, prepared microsponge is prepared by coating with electro conductive metal under specified condition of vacuum. Scanning probe moves over the surface of Microsponge and depicts image, from which topographical study of Microsponge can be performed [44,45].

X-ray Diffraction Study (XRD)
XRD is used to study physicochemical structure of given sample. Sample of Microsponge was subjected to equipment. Short wavelength radiation, X-ray is imparted to sample under specified condition of voltage. Diffracted radiation is recorded on diffractogram. Upon, analysing diffraction pattern, it can be concluded that weather structure of sample is amorphous or crystalline in nature. Further, from study, it can also be concluded that during processing, physical structure of drug or Microsponge has been changed or not [46,47].

Percentage Yield
Amount of drug, Polymer and other excipients forms a total theoretical mass of Microsponge. Practical mass of Microsponge is actually weight of Microsponge obtained after experimental process to prepare Microsponge. Percentage yield for Microsponge can be calculated using following formula [48,49]. % = [particle mass of microsponges/ Theoretical mass] × 100

CONCLUSION
Microsponges are versatile dosage form that can offer the incorporation of wide range of drug and dose of drug to be incorporated. High porosity of Microsponge imparts rapid drug release. Modified polymer can also be used to have sustained/ controlled drug delivery also. Compared to currently available treatment of Rheumatoid arthritis as Oral formulation, Microsponge can be designed to deliver the anti rheumatoid drug for topical application. This can have added advantage for site specific drug delivery. Furthermore, topical delivery can enhance efficacy, safety of dosage form. Future perspective for development of Microsponge for topical application can be promising route for management of arthritis.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.