REVIEW ON MICROSPONGE LEADING MICROPOROUS PARTICULATE TECHNOLOGY WITH CONTROLLED RELEASE, IMPROVE STABILITY TO PROVIDE OPTIMUM SKIN DISORDERS MANAGEMENT ENVIRONMENT FOR THERAPEUTIC APPLICATIONHTML Full Text
REVIEW ON MICROSPONGE LEADING MICROPOROUS PARTICULATE TECHNOLOGY WITH CONTROLLED RELEASE, IMPROVE STABILITY TO PROVIDE OPTIMUM SKIN DISORDERS MANAGEMENT ENVIRONMENT FOR THERAPEUTIC APPLICATION
Nishu Tomar 1, Neelam Pawar * 1 and Kavita Bahmani 2
Department of Pharmaceutical Sciences 1, Chaudhary Bansi Lal University, Bhiwani - 127021, Haryana, India.
Department of Pharmaceutical Sciences 2, Guru Jhambheswar Univerity, Hisar - 125001, Haryana, India.
ABSTRACT: Although serious systemic and cutaneous side effects need a novel delivery system that provides prolonged and controlled drug release, minimum systemic drug absorption with reduced side effects. Microsponge, a drug delivery system, possesses the versatility to load a wide range of active ingredients to facilitate the controlled release of active ingredients to reduce systemic exposure and to reduce side effects. Microsponges are polymeric sponges that consist of interconnecting voids with a non-flexible structure with a porous surface. Microsponge delivery technique provides extended product stability, enhanced safety, enhanced formulation flexibility, enhanced product efficacy, enhanced aesthetic appeal with reduced side effects. Therefore, this review provides an overview of microsponge technology with its methodology, mechanism, programmable release, and characterization of the microsponge delivery system. Review compiled recent data regarding marketed formulation, their applications, and the list of patents. This review also contains validation, stability guidelines, and examples of drug release profiles from microsponges. Microsponges are frequently used for topical use but recently used for oral use.
Controlled release, Drug delivery, Microsponges, Stability, Validation
INTRODUCTION: Deceive a privileged drug concentration due to the microsponge drug delivery system which contains interconnecting networks and pores leads to control release rate, and target drugs to a particular body site comprise 1. Won in 1987 developed microsponge technology, which was further patented as an advanced polymer that is useful for a prescription pharmaceutical product, cosmetics and over the counter product 2.
These delivery systems contain porous polymeric structure sponge-like sphere particle with interconnecting voids inside its non-flexible configuration and hefty porous surface, which releases the drug in a controlled manner 3. Various pharmaceutical formulation developed through possible headed integration of microsponge like; gels, emulsions, tablets, and capsules. The micro-sponges have subsequent properties: size range - 5-300 μm in diameter, 1μm sphere contains 10000 pores, pore volume – 0.1 – 0.3cm3/g, and internal-pore structure - 10 ft. in length (20 to 500m2/g).
Microsponge application, as a controlled topical delivery system needed to be developed for the following reason, which is shown in Fig. 1.
FIG. 1: CONTROL RELEASE OF MICROSPONGES IS REQUIRED IN THE ABOVE MENTIONED CONDITIONS
The objectives of microsponges formulation are to grasp drug ingredients in a circumscribed atmosphere. Endow with controlled deliverance of oral medication to the lower gastrointestinal (GI) tract. Improve the solubility of feebly water-soluble drugs through entrapment in the microsponge system pores. Boost the dissolution of the drug. Lessen the irritation at the site of the application.
The active ingredient to be entrapped into microsponge should have the following properties, as shown in Fig. 2 6-8.
FIG. 2: DRUG PROPERTIES TO ENTRAP IN MICROSPONGES
Microsponges strategy with following potential advantage over other delivery systems as listed in Fig. 3. 7-11
FIG. 3: ADVANTAGES OF MICROSPONGES DRUG DELIVERY SYSTEM
1. Method of Preparation of Microsponges: Entrapment of drug substance into microsponge particles mostly done by two methods namely (one-step process or by two-step process): Quasi-Emulsion Solvent Diffusion method and Liquid-Liquid Suspension Polymerization method
1.1. Quasi-Emulsion Solvent Diffusion Method: In this method, the former two phases (external and internal phase) is prepared. The external phase consists of organic solvents and distilled water containing surfactants and internal phase containing drug, polymer, solvent, and plasticizer. The Quasi-Emulsion Solvent Diffusion is a two-step process, as shown in Fig. 4. 11-14
FIG. 4: QUASI-EMULSION SOLVENT DIFFUSION
1.2. Liquid-Liquid Suspension Polymerization Method: Microsponges is primed by liquid-liquid suspension polymerization method; in this procedure, initially, the monomer and active ingredient assorted into an appropriate solvent subsequent to that the muddle solution is dispersed in the aqueous phase containing (surfactants) with the agitation. Throughout the polymerization progression, the solvent is distant, and spherical porous microsponges are formed, which is shown in Fig. 5 as follows 12-16.
FIG. 5: LIQUID-LIQUID SUSPENSION POLYMERIZATION METHOD
Mechanism: Drugs should not be too much soluble in the preferred vehicle, so it is important that formulating vehicles for the proposed mechanism throughout compounding of refined products should less to endow benefits of control steady release. Alternatively addition of drugs in solvent in liberated form and device solvents which has nominal solubilizing power for microsponge entrapment. Release mechanism triggered by a shift in equilibrium from microsponge polymer to carrier vehicle provides an initial loading dose of the drug before releasing in microsponge entrapment. The drug release rate depends on the partition coefficient between polymer and solvent, surface area, mean pore diameter, moisture, pH, temperature, and pressure 16-17.
The details of the mechanism of action showed in Fig. 6 and 7 as follows:
FIG. 6: MECHANISM OF ACTION OF MICROSPONGE FORMED
FIG. 7: DRUG SUBSTANCE RELEASE FROM MICROSPONGE AT THE SITE OF ACTION
2.1 Factors Affecting Release Mechanism:
2.1.1 Pressure Triggered Systems: When microsponge formulation rubbed on-site release its entrapped material. The pressure trigger system depends on characteristics of sponge formed, nature of material entrapped, process, and formulation variables.
2.1.2 Temperature Triggered Systems: By increasing the temperature flow rate of active ingredient encumbered in microsponge can be enhanced especially when excessively tacky material entrapped. Feasibility increase in temperature can increase in the release of active from microsponge.
2.1.3 pH Triggered Systems Formulation pH depends on the site of the same application pH triggers the release rate of active ingredient this can be achieved by modifying coating of microsponge.
2.1.4 Solubility Triggered System: Microsponge encumbered with hydrophilic ingredients that deliver active ingredients in the existence of water. This release rate depends on the capability of the external medium to suspend the active, the concentration gradient, or the capability to puff up the microspore network 8-9, 17-19.
The increased release of entrapped drug with several factors shown in Fig. 8.
FIG. 8: FACTORS AFFECTING RELEASE OF DRUG FROM MICROSPONGE FORMULATION
Methods of Drug Release: The methods for analyzing drug release from microsponges and permeation through the skin are divided into three categories, as shown in Fig. 9 20-21.
FIG. 9: METHOD ADOPTED FOR STUDY OF DRUG RELEASE FROM MICROSPONGE FORMULATION
Research on Prepared Microsponges: Recent research on microsponge delivery technique summarized in Table 1, which contains drugs, polymers, solvent, method of preparation with results as shown below:
TABLE 1: SUMMARY OF RECENT RESEARCH ON MICROSPONGES DRUG DELIVERY SYSTEM
|Author||Drug used||Polymer used||Solvent used||Method of preparation||Result|
|Rekha et al.,
|Mometasone furoate||Eudragit RS-100||Dichloromethane and Ethanol||Quasi emulsion solvent diffusion||Increasing the ratio of the drug: polymer will decrease the release rate of the drug from microsponges 22|
|Swetha et al.,
|Etodolac||Ethylcellulose, Eudragit RS100||Dichloromethane and Ethanol||Quasi emulsion solvent diffusion||Formulation of Etodolac with Ethylcellulose give the maximum drug release 99.3% within 8 h 23|
|Maiti S et al., (2011)||Diclofenac sodium||Ethylcellulose||Dichloromethane||Quasi emulsion solvent diffusion||Increasing the drug and polymer ratio will increase their release rate followed Higuchi diffusion kinetic 24|
et al., (2012)
|Acyclovir sodium||Ethylcellulose||Dichloromethane||Emulsion solvent diffusion method||Optimized F1 released 50.85% drug at 8 and Ficks law of diffusion not followed 25|
|Karthika R et al., (2013)||Lornoxicam||Eudragit RS 100||Ethyl alcohol||Quasi- emulsion solvent diffusion||Drug releases follow First-Order kinetic and mechanism followed Hixson- Crowell model 26|
|Sonali et al., (2014)||Prednisolone||Eudragit RS 100||Ethyl alcohol||Quasi- emulsion solvent diffusion||Cumulative release of microsponges 48-87%
at 8 h 27
|Hamid Hussain et al., (2014)||Diclofenac sodium||Ethylcellulose||Dichloromethane||Quasi emulsion technique||The drug content of different formulations was found from 19.07 to 33.09. 28|
M. Osmani et al., (2015)
|Domperidone||Eudragit RS100||Dichloromethane||Quasi- emulsion solvent diffusion||Drug- Polymer ratio of 1:2 more efficient and 76.38%
drug releases at 8 h 29
|Rajurkar VG et al., (2015)||Naproxen||Eudragit RS100||Dichloromethane and Ethanol||Quasi- emulsion solvent diffusion||Increase in the ratio of the drug: polymer resulted in control release rate of naproxen from microsponges 30|
|Atmaram P et al., (2015)||Oxybenzone||Ethylcellulose||Dichloromethane||Quasi- emulsion solvent diffusion||Controlled release of drug from microsponges promote the retention of drug with reduced permeation activity 31|
|Pande VV et al., (2015)||Sertaconazole nitrate||Eudragit RS- 100||Dichloromethane||Quasi- emulsion solvent diffusion||Batch F5 releases 69.38%drug at 8 hrs. that followed Zero-Order kinetics 32|
|Moin A et al., (2016)||Fluconazole||Eudragit S-100||Ethanol and Dichloromethane||Quasi- emulsion solvent diffusion||Microsponges loaded gel releases 85.38%drug at 8 h 33|
S et al., (2016)
|Famotidine||Eudragit RS-100||Dichloromethane||Quasi- emulsion solvent diffusion||% Entrapment efficiency was 88.83% and % cumulative release 86.9% for F6formulation 34|
|Shapali A et al., (2016)||Bifonazole||Propylene Glycol||Dichloromethane & Polyvinyl alcohol||Quasi- emulsion solvent diffusion||80.71%drug release of an optimized batch at the end of 24 h 35|
|Bhandare CR et al., (2016)||Risperidone||Ethylcellulose and Eudragit RS 100||Ethyl alcohol||Quasi- emulsion solvent diffusion||Ethylcellulose and Eudragit gave better drug release and encapsulation efficiency as compared to their single-use 36|
|Mohanty D et al., Q( 2016)||Betamethasone||Eudragit RS 100||Ethanol and Dichloromethane||Quasi- emulsion solvent diffusion||a pH of microsponges gel was6.8 and 73% drug release 37|
|Naji GH et al., (2017)||Piroxicam||Eudragit RS, RL, S -100||Dichloromethane and Ethanol||Quasi- emulsion solvent diffusion||Piroxicam micro sponge carbopol 934 gel produced a significant (p<0.05) improvement of the in-vitro release than pure piroxicam gel 38|
|Selvapriya A et al., (2017)||Nateglinide||Eudragit RS 100||Dichloromethane||Quasi- emulsion solvent diffusion||Microsponge with drug-polymerr ratio 1:3 was more proficient to give controlled release at the end of 12 h 39|
MF et al., (2018)
|5-Fluorouracil||Eudragit RS 100||Acetone||Oil in oil emulsion solvent diffusion||MS loaded 5-FU was more effective than 5-FU itself 40|
|Patil N et al., (2018)||Ritonavir||Ethylcellulose||Dichloromethane||Quasi- emulsion solvent diffusion||Drug release of 50.32% at the end of 10 h 41|
5. Characterization of Microsponges: Various methods are used for the characterization of microsponges.
5.1 Preformulation Studies: Preformulation is an assemblage of studies to predict physicochemical properties of a new drug substance that variable drug performance and important parameters for the development of a dosage form and formulation aspects. The Group of studies before formulation development is stated in Fig. 10 42-44.
FIG. 10: BRIEF SUMMARY OF PREFORMULATION STUDIES
5.1.1 Particle Size and Size Distribution: Particle size distribution testing done by using laser diffraction, microfluidic resistive pulse sensing, electro zone, single-particle optical sensing, sieve analysis, dynamic light scattering, air permeability diameter and nanoparticle tracking analysis. Particle size analysis designed to evaluate and report information about the size and range of a set of particles that affect the texture of formulation, predict material representation. Controlling particle size distribution attributes free-flowing properties of the powder and decreases agglomerates or polymerization at most important handling, packing, research quality control, and product development. Particle size analysis of loaded and unloaded microsponge can be performed by laser light diffractometry, mean size range, cumulative percentage drug release of microsponge of different particle size can be performed 45-51.
5.1.2 Compatibility Studies: Compatibility studies of drug-excipients are carried out to ensure that a finished dosage form does not show any unplanned reaction. Compatibility studies testing done by differential scanning calorimetry, powder X-ray diffraction, isothermal microcalorimetry, differential thermal analysis, isothermal stress testing, Fourier transform infrared spectroscopy, scanning electron microscopy, hot stage microscopy, thin layer chromatography, high-performance thin layer chromatography and solid-state nuclear magnetic resonance spectroscopy 45-52.
5.1.3 Morphology and Surface Topography of SPM: Available techniques for morphology and surface topography of microsponges are photon correlation spectroscopy (PCS), Scanning electron microscopy (SEM), transmission electron micro-scopy (TEM). Microsponges are encrusted by gold-palladium at 25°C - 27°C in an argon atmosphere, so surface morphology of microsponges is evaluated 45-54.
5.1.4 Determination of Loading Efficiency and Production Yield: Loading efficiency means quantity of drug encumbered per unit weight of microsponges. The loading efficiency of the microsponges can be done by using the following equation 45-51.
Loading efficiency = Actual drug content in microsponges / theoretical drug content
For calculating % loading efficiency, the above equation should be multiplied by 100.
The production yield of microsponges are determined by using the following equation:
% Production yield = Production yield / theoretical mass (polymer + drug) × 100
5.1.5 Polymer / Monomer Composition: Microsponge releases active constituents depends on particle size, drug loading, and polymer composition. The release rate of microsponges exaggerated by polymer composition due to change in partition coefficient between polymer and vehicle.
By intrigues, a graph of cumulative % release of the drug against time, the release rate of microsponges can be determined. Appropriateness of monomer combination with a drug will be screened for studying drug release profile 45-51.
5.1.6 Resiliency: Visco-elastic properties of microsponges should be optimized as per the requirement of the finished dosage form. The release rate of microsponges will be slower due to greater cross-linking. Release rate can be calculated by plotting graph of drug release against time 45-51.
5.1.7 Bulk and Tapped Density, Hausner’s Ratio, Carr’s Index, Angle of Repose: The tapping method is used for calculating the tapped density and % compressibility index. Angle of repose (θ) of the micro microsponges is determined by fixed funnel method, tilting box method, and rotating cylindrical method and other parameters are calculated by using following equation 55:
- Bulk density = Mass of Microsponges / Volume of microsponges before tapping
- Tapped density = Mass of Microsponges / Volume of microsponges after tapping
- Hausner’s ratio = Tapped density / Bulk density
- Carr’s index = (Tapped density- Bulk density) / Tapped density × 100
- Angle of repose (θ) = tan-1 (h/r)
Where, h = Height of the powder cone and r = Radius of powder cone.
5.1.8 Determination of Encapsulation Efficacy: The encapsulation efficacy of microsponges means %age of active constituents entrapped into microsponges, which is calculated by following equation 45-51.
Encapsulation efficacy = Actual drug content/ Theoretical drug content × 100
5.1.9 Diffusion Test: Franz diffusion cell is used for measuring drug release from microsponges. Membrane from animal skin (rat abdominal skin, mouse skin, and mucin) and artificial membranes (cellulose acetate and silastic) are used for determining dug release and permeation profile. Microsponge formulation is applied on membranes in donor compartment, and diffusion studies are studied by using phosphate buffer as a dissolution medium in receptor compartment at 37 ± 1 °C 58-59.
5.1.10 Stability Studies: Stability studies of micro-sponge in order to predict and ensure shelf life for acceptance and approval of microsponge based formulation over different time periods, temperature and humidity conditions.
Types of Stability: Chemical stability, physical stability, microbiological stability, therapeutical stability and toxicologic stability. Stress testing includes effects of temperature, humidity, photo-lysis and oxidation on drug substances. Photo-stability is also a part of stress testing. The selection of batches includes three primary batches; these batches should be manufactured to a minimum pilot scale by the same procedure involved in the final production batch. The specification contains a list of tests, reference to analytical procedures, and proposed acceptance criteria. Stability studies include testing of those attributes of the drug substance that are susceptible to change during storage and possibly to influence quality, safety and/or efficacy.
Frequency of testing for drug substances with a planned re-test period of at least 12 months, the frequency of testing for long term storage condition should be every 3 months over the first year, every 6 months over the second year, and annually thereafter through the proposed re-test period. Four ICH stability climatic zones are described for the purpose of assessment of stability worldwide as follows in Tables 2, 3, 4, and 5 56-57.
TABLE 2: WORLDWIDE TEMPERATURE ZONE WITH TEMPERATURE AND HUMIDITY CONDITION
|S. no.||Zone||Climate||Temperature Condition|
|T||Zone I||Temperate zone||21 °C ± 2 °C|
|2.||Zone II||Mediterranean zone||25 °C ± 2 °C|
|3.||Zone III||Hot and dry zone||30 °C ± 2 °C|
|4.||Zone IV||Hot and humid zone||30 °C ± 2 °C|
|5.||Zone IVb||ASEAN testing
condition hot/higher humidity
|30 °C ± 2 °C|
TABLE 3: STORAGE CONDITION IN GENERAL CASE
|Study||Storage condition||Minimum time period covered by data at submission|
|Long term||25°C ± 2°C/ 60% RH ± 5% RH Or 30°C ± 2°C/65% RH ± 5% RH||12 months|
|Intermediate||30°C ± 2°C/ 65% RH ± 5% RH||6 months|
|Accelerated||40°C ± 2°C/75% RH ± 5% RH||6 months|
TABLE 4: DRUG SUBSTANCES INTENDED FOR STORAGE IN A REFRIGERATOR
|Study||Storage condition||Minimum time period covered by data at submission|
|Long term||5°C ± 3°C||12 months|
|Accelerated||25°C ± 2°C/60% RH ± 5% RH||6 months|
TABLE 5: DRUG SUBSTANCES INTENDED FOR STORAGE IN A FREEZER
|Study||Storage condition||Minimum time period covered by data at Submission|
|Long term||- 20°C ± 5°C||12 months|
5.1.11 Statistical Analysis: The records be prevalent from all testing were subjected to statistical examination by Student t-test and one-way analysis of variance (ANOVA) via Graph Pad Instate software 45-51.
6. Drug Delivery from Microsponges:
6.1 Methodologies Applied: Methodology reliant on the drug and the dosage form. The drug influences the predilection of the receiver medium, whereas the dosage form does the temp. of analysis and equipment to be used.
The control of the temperature is extensive to stimulate the application site of dosage forms. Oral and suppository dosage form should be evaluated at 37 °C to mimic the body temperature. Topical formulations usually evaluated at 32 °C, the temp. of the skin. The stirring speed generates a flux which alters the liquid/solid interface stuck between solvent and drug. In order to maintain a reproducible laminar flow, the stirring should be maintained at a moderately low rate.
Most frequently used apparatuses are static and used to inspect the drug release profile from microsponges are:
- USP apparatus 1
- USP apparatus 2
- Vertical diffusion cell
- Modified Rossett-Rice cell 1, 60-6
6.2. Kinetic Models: To figure out the control mechanism of drug release, in-vitro data of release profile have been used to authenticate the integrity of the kinetic equation.
6.2.1. Zero-Order Kinetics: Deﬁnes a system in which the release of drugs is a function of time only. The process is autonomous of active concentration and proceeds at a constant rate.
Qt = Q0 + k0.t
Where Qt is the amount of drug dissolved in time t, Q0 is the initial amount of drug, k0 is the zero-order constant.
First-order defines a system that alteration relies on concentration gradient with time. A straight line will be obtained as a result with a slope of kt/2.303 and intercept at t = 0 of log Q0.
Log Qt = logQ0 + k1.t/2.303
6.2.2 The Higuchi Model: Describes a system in which amount of drug release and the square root of time is proportional to each other
Q t / Q∞ = k.t1/2
Where Q∞ is the cumulative amount of drug released at the inﬁnite, k1 is the ﬁrst-order constant.
6.2.3 Korsmeyer and Peppas Model: Defines a system that is helpful in the case of multiple phenomena.
Mt / M∞ = k.tn
Where Mt and M∞ are cumulative quantity of drug release at time t and inﬁnite time, k is the constant incorporating structural and geometrical characteristics of cumulative release device, n is a diffusion release exponent investigative of the mechanism of drug release for drug dissolution. Examples of the drug showing different kinetics are as shown in Fig. 11 1, 62-63.
FIG. 11: DRUG SHOWING DIFFERENT KINETICS
It is possible to set up a classiﬁcation of realistic behavior, according to n-value. Thus, n <0.5 designates the release that is governed with Fickian diffusion, in which the diffusion is superior to the progression of polymeric sequence relaxation.
n = 1 designate the release that is controlled merely via respite of polymeric chains and notorious as swelling (transport case II).
Values between 0.5 and 1.0 designate an unexpected transport (non-Fickian kinetics), subsequent to the phenomenon of both diffusion and swelling processes.
Kinetics of super case II characterized by n values more than 1, the effect of n values on the release mechanism of microsponges as shown in Fig. 12 64-66.
FIG. 12: EFFECT OF CARBOMERS AND N-VALUES ON RELEASE MECHANISM OF MICROSPONGES
5.15. Drug Release Studies: Microsponge releases active constituents in a précised amount in a specified time period due to the presence of interrelated channels. The relationship among the microsponge physical properties and the polymers are used for preparing microsponges, which influence the size and number of interrelated channels in microsponge, which ultimately influence the release rate of microsponges as shown below in Fig. 13 & 14 67-68, 36, 66, 69.
FIG. 13: EFFECT OF POLYMER RATIO ON RELEASE RATE OF MICROSPONGES
FIG. 14: EFFECT OF POLYMERS ON RELEASE RATE OF MICROSPONGES
7. Preclinical Studies: Preclinical studies include in-vivo animal models to identify microsponge based formulation initial safe dose and safety parameters. Type of preclinical testing includes short term animal study (acute) and long term animal studies (chronic). Acute studies to determine pharmacological action and toxicity and whereas chronic studies look for potential side effects and for reproductive effect. Preclinical trials are required for the regulatory body and also check for a kinetic profile of drug and selection of administration route.
8. Skin Irritation Study: The study protocol of skin irritation study approved from Institutional review board of India through institutional animal ethics committee other regulation like Declaration of Helsinki, the guidance of good clinical practice, ICH of the technical requirement for registration of pharmaceutical for humans and EMEA, CPMP/ICH/135/95JULY2002 give guidance for skin irritation studies.
Test microsponge based formulation has to be applied to an area of approximately 6cm2 of skin and covered with gauze patch for 1 h. After 1 h, gauze is removed, and response is recorded. Same observation make under the application of controls.
The mean erythemal scores are recorded according to Draize in which 0 means no erythema, 1 means slighter erythema, 2 means moderate erythema, 3 means moderate to severe erythema, 4 means severe erythema.
9. Anti-inflammatory Activity by Ear Edema Measurement: After approval of the Animal Ethical Committee in accordance with CPCSEA guidelines. The anti-inflammatory activities are conducted with the use of male Swiss mice (25-35g), which is housed at 22 ± 2 °C under 12 h light and 12 h dark cycle. Induced edema in right ear with microsponge formulation of the amount per ear of cotton oil dissolved in 20 ml acetone. Measure thickness before and after 6 h of induction of inflammation by use of digital Vernier caliper and prepare result report documents 70-71.
10. Validation of Microsponges: The perception of validation was introduced in order to improve the eminence of pharmaceuticals. Process validation is stated as troup and analysis of data from the process design stage during the production. Process validation confirms that a process produces a product of a determined standard and quality characteristics.
10.1. Process Validation Reports Contains: Product name, generic name, label claim, shelf life, batch size, no. of batches selected for study, batch no., batch manufacturing record no. and master formula record no.
10.2. Contents for Process Validation: Content should contain title, objective, scope, response-bility, references, batch selected for study, list of equipment, sampling plan, sampling detail, standard batch formulation, raw material details, flow diagram for manufacturing and packing, operation, cleaning, line clearance, area clearance, equipment clearance, environmental monitoring, preparation, filling, evaluation, crimping and coding, packing, summary and conclusion, approval, the preliminary approval, final approval.
10.3. Title and Objective: Process validation of microsponge formulation and determination of process by continually running the system and record all significant information and data.
10.4. Scope: To be performed when there is a change in Mfg. process or formula, equipment used, Mfg. site/location.
10.5 Batch Selected for Study: Firstly, three batches will be selected and maintain a record with manufacturing date, expiry date, and batch size.
10.6 List of Equipment: Electronic weighing balance, Stirrer, Homogenizer, Hot air oven, UV- Spectrophotometer, Zetasizer, Differential scanning Calorimetry (DSC), X-ray diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR) and pH meter.
10.7 Area Clearance: Cleanliness of the area, cleanliness of process control equipment.
10.8 Equipment Clearance: Physically check clearance of equipment, check wash water report, sterilization of equipment.
10.9 Environment Monitoring: Environmental condition should be maintained during the processing of microsponges as follows: Tempe-rature - 25 ± 2 °C, Pressure - 6-15 Pascal, Relative Humidity - 50 ± 5%.
10.10 Evaluation: Preformulation studies, Particle size and size distribution, Compatibility studies, Morphology and Surface topography of SPM, Determination of loading efficiency and production yield, Polymer / Monomer composition, Resiliency, Bulk and tapped density, Haussner’s ratio, Carr’s index, Angle of repose, Dissolution tests, Determ-ination of encapsulation efficacy, Stability studies, Statistical analysis and safety considerations- Skin irritation studies in rabbits, anti-inflammatory activity by ear edema measurement.
10.11. Summary and Conclusion: Process validations of 3 batches should be completed successfully. All the data should be reviewed and concluded that.
10.12 Cleaning Stage: Data from the cleaning stage indicates that all the parameters and analytical results are lies well within specification. Hence the stage will be validated.
10.13. Bulk Manufacturing Stage: Data from the manufacturing stage indicates that all the parameters and analytical results are lies well within specification. Hence, the stage will be validated 72.
Marketed Formulation: Microsponge delivery technique at the moment employed in a huge number of products vend by various cosmetic and toiletry companies.
Table 5 summarizes the marketed formulation with their brand name, drug, treatment, advantages, and manufacturer, as shown as follows 25, 73.
Intellectual Prospect of Microsponge Drug Delivery System: A number of patents were documented on the microsponge drug delivery system none of them deals with oral drug delivery. Patented MDS was used by advanced polymer systems for enhancing the safety, efficacy, and visual eminence of various products such as Tretinoin, Dimethicone, Salicylic acid, etc.
A patent on collagen microsponges was disclosed by Dean et al., in 1989 for immobilizing micro-sponges. Another patent includes microsponge impregnating non-wovel towel invented by Love et al., in 2008, biodegradable photocatalytic nano-composite microsponges of Polylactic acid by Eugenia et al., in 2017, etc.
Proprietary technology was developed by AP Pharma using porous alginate microspheres with macromolecules like (vaccines and peptides) for oral controlled delivery. The company is conducting clinical trials for these carriers as a vehicle to deliver agents to lower G.I.T. by developing a composite tablet design with active ingredients loaded in microsponges 76.
Recent Advancement in Microsponge Drug Delivery System: Diverse advances in micro-sponge drug delivery systems were prepared by modifying the methods to make nanosponges, nanoferrosponges, porous microspheres, and porous microbeads. Nanosponges were used for passive targeting of cosmetic agents and incorporation of hydrophobic and hydrophilic drugs for example β-cyclodextrin nanosponge. By increasing drug-polymer ratio, particle size will be reduced. The pore size in β-cyclodextrin nanosponge modulated by CD-PMA molar ratio.
Nanoferrosponges were prepared by co-precipitation of polymer and magnetite. Nanoferro-sponge have improved penetration at a specific site due to the outer magnetic trigger. The magnetic trigger penetrates carriers into deeper tissues and then the exclusion of magnetic substances from the particle parting the porous structure.
Polymerization and cross-linking were activated by heating in the High internal phase emulsion method for producing porous microbeads 7-18, 73-75.
TABLE 6: VARIOUS MARKETED FORMULATION BASED ON MICROSPONGES DELIVERY TECHNIQUE
|Name of Product||Drug||Treatment||Advantages||Manufacturer|
|1||Cream||Retin-A- Micro||Tretinoin||Acne vulgaris||0.17 & 0.04% tretinoin entrapped into a microsponges containing methylmethacrylate/ glycol & dimethylacrylate polymers||Ortho-McNeil Pharmaceuticals, Inc.|
|0.5% Fluorouracil incorporated into a microsponge composed of glycoldimethacrylate / methyl methacrylate and dimethicone||Dermik Laboratories Inc.|
|Light weight cream delivers both immediate and time-released wrinkle fighting action||Avon|
|4||Cream||Retinol 15 Night cream||Retinol||Anti-
|Retinol 15 Nightcream result in the visibled iminishment offine lines and wrinkles, improve skin discoloration.||Biomedic, Sothys|
|Green Tea||Sunscreen||Oil free formula containing green tea with cornstarch and vinyl dimethicone||Dermalogica|
|6||Cream||EpiQuin micro||Hydroquinone& Retinol||Hyper pigmentation||Microsponges release active ingredients into the skin gradually throughout the day which minimize skin irritation||Skin MedicaInc|
|7||Gel||Salicylic peel 20 & 30||Salicylic acid||Excellent Exfoliation||Excellent exfoliation and stimulation of the skin which improve fine lines, pigmentation & acne concerns||Biomedic|
|8||Moisturizing Cream||LactrexTM 12%
|Lactic acid & Ammonium lactate||Moisturizer||Moisturize dry, flaky, cracked skin||SDR
|9||Lotion||Oil control lotion||Natural antibiotics||Tightness to promote healing, acne- prone, oily skin conditions||Absorb oil on the skin surface||Fountain Cosmetics|
|10||Spray||Aramis Fragrances||Antiperspirant spray gives sustained release of fragrance||Ultra light powder absorb fragrant oil easily||Aramis Inc.|
|11||Lotion impregnated Wipes||Ultra Guard||Dimethicone||Protects babies skin||Dimethicone that helps to protect babies skin from a diaper rash||Scott Paper|
|12||Cream||NeoBenz||Benzyl Peroxide||Anti-acne treatment||Reduce the amount of acne-causing bacteria by causing the skin to dry||Skin Media, Inc.|
Patents List on Microsponge: Patents number, inventors, and publication shown in Table 7 73.
TABLE 7: INVENTORY OF SEVERAL PATENTS FILED IN MICROSPONGES DRUG DELIVERY SYSTEM
|1||US4997753||Dean RC et al.||1991|
|2||US5135740||Katz et al.||1992|
|3||US5100783||Robert et al.||1992|
|4||US5679374||Fanchon et al.||1994|
|5||US5316774||Robert P et al.||1994|
|6||US5725869||Ray JR et al.||1996|
|7||US5851538||Forix M. et al.||1998|
|8||US6395300||Straub et al.||1999|
|9||US6211250||Tomlinson et al.||2001|
|10||US20030232091||Shefer et al.||2002|
|12||US20040247632||Cattaneo & Maurizio||2004|
|13||US20050271702||Steven G et al.||2005|
|14||US7098315||Schaufler A et al.||2006|
|17||US7426776||Franklin SL et al.||2008|
|22||US8361273||Ferring BV et al.||2013|
|23||US8758728||Stiefel Research Australia Pty Ltd.||2014|
|24||US8936800||Galderma Research & Development||2015|
|25||US9764316||Eugenia P et al.||2017|
Microsponge Approach in Future Prospective: As a novel drug delivery system besides use as topical delivery of drugs, micro-sponge can also use in controlled oral peptide delivery, tissue engineering in cell culture media (stem cell culture and cellular regeneration) and transdermal delivery system.
Developed formulation with prolonged stability, without the use of preservatives, extended-release, reduce irritation. Microsponge technology act as carrier system in cosmetics, toothpaste or mouthwash, long lasting colored cosmetics, lipsticks and covering powder.
We can develop for alternative drug administration route like parenteral and pulmonary route1-2, 4-11, 18, 73-75.
Application of Microsponge: Application of microsponge drug delivery system from topical route and oral route as shown in Table 8 and 9 6-14, 25, 73-75.
TABLE 8: TOPICAL DRUG DELIVERY USING MICROSPONGE TECHNOLOGY
|Antifungal||Fluconazole, Miconazole, Clotrimazole, Econazole||Give sustained release of drugs.|
|Antidandruff||Selenium Disulfide, Zinc Pyrithione||Enhanced safety and efficacy of drugs with reduced irritation and odor|
|Anti-acne||Tretinoin, Benzoyl Peroxide||Reduce skin irritation and sensitization.|
|Anti-wrinkle||Retinol||Time-released delivery into the skin|
|Anti-inflammatory||Piroxicam, Hydro-cortisone||Extended drug release with reduced dermatoses and allergy|
|Anti-actinic Keratoses||5-Fluorouracil||Treat actinic keratoses with the reduced dosage form.|
|Skin depigmentation||Hydroquinone||Improve aesthetic appeal with reducing oxidation.|
|Moisturizer||Lactic acid and ammonium lactate||Moisturize dry, cracked and flaky skin|
TABLE 9: ORAL DRUG DELIVERY USING MICROSPONGE TECHNOLOGY
|Anti-inflammatory||Indomethacin||Reducing side effects like G.I. irritation with modified release|
|Anti-pyretic||Paracetamol||Time-release dosage form with a pH-dependent polymer coating|
|Anticholinergic||Dicyclomine||Effective local action with prolonged drug release|
|Colon targeting||Paracetamol||Time-release dosage form with a pH-dependent polymer coating|
|Musculoskeletal pain||Ketoprofen||Provided modified-release wit reducing the severity of side-effects|
CONCLUSION: The Microsponge, drug delivery system, is a flexible approach complemented by novel dosage form development approach in pharmaceutical, cosmeceutical, and biopharmaceutical products. Interconnecting pores in microsponge responsible for the release of active constituents in a controlled manner. The Microsponge, drug delivery system, perks up the stability of incompatible constituents devoid of using any preservatives. For cosmetics perspective, microsponge delivery technique is advanced among other delivery techniques due to the porous nature of microsponge, which offers oil controlling property. So, a micro-sponge delivery system offers various advantages; therefore, MDS is a promising meadow that needs to be scrutinized for further research.
ACKNOWLEDGEMENT: The authors are greatly thankful to Belco Pharma (Bahadurgarh, Haryana) for providing gift samples of standard drugs. The author also wishes to thank supervisor Mrs. Neelam for her support and guidance throughout the research work.
CONFLICTS OF INTEREST: The authors confirm that this article content has no conflict of interest.
- Junqueira MV and Bruschi ML: A review about the drug delivery from microsponges. AAPS Pharm Sci Tech 2018; 4: 1501-11.
- Kaity S, Maiti S, Ghosh AK, Pal D, Ghosh A and Banerjee S: Microsponges: a novel strategy for drug delivery system. Journal of Advanced Pharmaceutical Technology & Research 2010; 1: 283-90.
- Lalitha SK, Shankar M, Likhitha D, Dastagiri J and Babu MN: A current view on microsponge drug delivery system. Eur J Mol Biol Biochem 2016; 2: 88-95.
- Patel SB, Patel HJ and Seth AK: Microsponge drug delivery system: an overview. J Global Pharm Tech 2010; 8: 1-9.
- Moin A, Deb TK, Osmani RA, Bhosale RR and Hani U: Fabrication, characterization, and evaluation of microsponge delivery system for facilitated fungal therapy. Journal of Basic and Clinical Pharmacy 2016; 7: 39-48.
- Mandava SS and Thavva V: Novel approach: microsponge drug delivery system. International Journal of Pharmaceutical Sciences and Research 2012; 3: 967-80.
- Aloorkar NH, Kulkarni AS, Ingale DJ and Patil RA: Microsponges as innovative drug delivery systems. International Journal of Pharmaceutical Sciences and Nanotechnology 2012; 5: 1597-1606.
- Patil RS, Kemkar VU and Patil SS: Microsponge drug delivery system: a novel dosage form. Am J Pharm Tech Res 2012; 2: 2249-3387.
- Bamane GS, Kakade TB, Metkari VB and Kulkarni LV: Microsponges: a novel drug delivery system. World J. Pharm. Pharm. Sci 2014; 3: 748-62.
- Kappor D, Patel M, Vyas RB, Lad C and Tyagi BL: A review on microsponge drug delivery system. Journal of Drug Delivery and Therapeutics 2014; 4: 29-35.
- Bhimavarapu R, Devi R, Nissankararao S, Devarapalli C and Paparaju S: microsponges as a novel imperative for drug delivery system. Asian Journal of Research in Chemistry 2013; 6: 842.
- Kumar S, Tyagi LK and Singh D: Microsponge delivery system (MDS): A unique technology for delivery of active ingredients. IJPSR 2011; 1: 12.
- Patel EK and Oswal RJ: Nanosponge and microsponges: a novel drug delivery system. Int J Res Pharm Chem 2012; 2: 237-44.
- Arora N, Agarwal S and Murthy RS: Latest technology advances in cosmaceuticals. International Journal of Pharmaceutical Sciences and Drug Research 2012; 4: 168-82.
- Aldawsari H and Badr-Eldin SM: Microsponges as promising vehicle for drug delivery and targeting: Preparation, characterization and applications. African Journal of Pharmacy and Pharmacology 2013; 7: 873-81.
- Pandey P, Jain V and Mahajan SC: A review: microsponge drug delivery system. International Journal of Biopharmaceutics 2013; 4: 225-30.
- Osmani RA, AloorkarNH, Kulkarni AS, Harkare BR and Bhosale RR: A new cornucopia in topical drug delivery: microsponge technology. Asian J Pharm Sci Technol 2014; 4: 48-60.
- Joshi G and Rajandeep HK: Microsponges: A Novel Drug Delivery System. IRJPBS 2016; 3: 01-11.
- Lalitha SK, Shankar M, Likhitha D, Dastagiri J and Babu MN: A current view on microsponge drug delivery system. Eur J Mol Biol Biochem 2016; 3: 88-95.
- EmbilK and Nacht S: The microsponge® delivery system (MDS): a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release of actives. Journal of microencapsulation 1996; 13: 575-88.
- Almeida I and Costa P: Tissue-based in-vitro and ex-vivo models for dermal permeability studies. In Concepts and Models for Drug Permeability Studies 2016; 325-42.
- Castro P, Madureira R, Sarmento B and Pintado M: Tissue-based in-vitro and ex-vivo models for buccal permeability studies. In Concepts and Models for Drug Permeability Studies 2016; 189-202.
- Rekha U and Manjula BP: Formulation and evaluation of microsponges for topical drug delivery of mometasone furoate. International Journal of Pharmacy and Pharmaceutical Sciences 2011; 3: 133-37.
- Swetha A, Rao MG and Ramana KV: Formulation and in-vitro evaluation of etodolac entrapped in microsponge based drug delivery system. International Journal of Pharmacy 2011; 1: 73-80.
- Maiti S, Kaity S and Ray S: Development and evaluation of xanthan gum-facilitated ethyl cellulose microsponges for controlled percutaneous delivery of diclofenac sodium. Acta Pharmaceutica 2011; 3: 257-70.
- Chandramouli Y, Firoz S, Rajalakshmi R, Vikram A, Yasmeen BR and Chakravarthi RN: Preparation and evaluation of microsponge loaded controlled release topical gel of acyclovir sodium. Int J Bio 2012; 3: 96-102.
- Karthika R, Elango K, Ramesh Kumar K and Rahul K: Formulation and evaluation of lornoxicam microsponges tablets for the treatment of arthritis. International Journal of Pharmaceutical Innovations 2013; 3: 29-40.
- Sonali SR and Prajapati SK: Formulation and evaluation of prednisolone loaded microsponges for colon drug delivery: in-vitro and pharmacokinetic study. Int J Pharm Sci Res 2014; 5: 1994-2005.
- Hussain H, Dhyani A, Juyal D and Bahuguna A: Formulation and evaluation of gel-loaded microsponges of diclofenac sodium for topical delivery. The Pharma Innovation 2014; 3: 58.
- Osmani RA, Aloorkar NH, Ingale DJ, Kulkarni PK, Hani U, Bhosale RR and Dev DJ: Microsponges based novel drug delivery system for augmented arthritis therapy. Saudi Pharmaceutical Journal 2015; 5: 562-72.
- Rajurkar VG, Tambe AB and Deshmukh VK: Topical anti-inflammatory gels of naproxen entrapped in eudragit based microsponge delivery system. Journal of Advanced Chemical Engineering 2015; 5: 2-6.
- Pawar AP, Gholap AP, Kuchekar AB, Bothiraja C and Mali AJ: Formulation and evaluation of optimized oxybenzone microsponge gel for topical delivery. Journal of Drug Delivery 2015; 2: 147-59.
- Pande VV, Kadnor NA, Kadam RN and Upadhye SA: Fabrication and characterization of sertaconazole nitrate microsponge as a topical drug delivery system. Indian Journal of Pharmaceutical Sciences 2015; 6: 675.
- MoinA, Deb TK, Osmani RA, Bhosale RR and Hani U: Fabrication, characterization, and evaluation of microsponge delivery system for facilitated fungal therapy. Journal of Basic and Clinical Pharmacy 2016; 7: 39.
- Charagonda S, Puligilla RD, Ananthula MB and Bakshi V: Formulation and evaluation of famotidine floating microsponges. Int Res J of Pharmacy 2016; 4: 62-67.
- Bagde SA, Jadhav N, Mali N and Karpe M: Comparison of in-vitro Antifungal Studies of Different Bifonazole Formulations with Marketed Bifonazole Formulation. International Journal of Pharmaceutical Chemistry and Analysis 2015; 2: 182-86.
- Bhandare CR and Katti SA: Formulation of microsponges of risperidone HCl. Int J Res Pharm Chem 2016; 6: 518-27.
- Mohanty D, Bakshi V, Rashaid MA, Reddy TV, Dholakia NA and Babu AM: Design and in- vitro characterization of betamethasone microsponge loaded topical gel. International Journal of Pharma Research and Health Sciences Volume 2016; 4: 1124-29.
- Naji GH and Hameed SN: Study the effect of variables on piroxicam microsponge formulated as topical gel for transdermal drug delivery. Int. J. Pharm. Sci. Rev. Res. 2017; 42: 1241-49.
- Selvapriya A, Elango K, Kumari SD and Keerthana K: Formulation and evaluation of nateglinide microsponges for the treatment of type II diabetes mellitus. World Journal of Pharmacy and Pharmaceutical Sciences 2017; 6: 1685-94.
- Othman M, Zayed GM, El-Sokkary GH, Ali UF, Abdellatif A and Othman MH: Preparation and evaluation of 5-fluorouracil loaded microsponges for treatment of colon cancer. J Cancer SciTher 2017; 9: 307-13.
- Patil NS, Tadavi SA and Pawar SP: A research on formulation and evaluation of microsponge loaded in topical gel of ritonavir. Int J Pharm Pharm Sci 2011; 3: 133-37.
- Chaurasia G: A review on pharmaceutical preformulation studies in formulation and development of new drug molecules. International Journal of Pharmaceutical Sciences and Research 2016; 7: 2313.
- Desu PK, Vaishnavi G, Divya K and Lakshmi U: Pharmaceutical sciences. J Pharm Sci 2015; 2: 1399-1407.
- Kesharwani R, Ansari MS and Patel DK: Novel technology used in the preformulation study: a review. Journal of Drug Delivery and Therapeutics 2017; 4: 20-33.
- Niethard FU, Gold MS, Solomon GS, Liu JM, Unkauf M, Albrecht HH and Elkik F: Efficacy of topical diclofenac diethylamine gel in osteoarthritis of the knee. The Journal of Rheumatology 2005; 12: 2384-92.
- Orlu M, Cevher E and Araman A: Design and evaluation of colon specific drug delivery system containing flurbiprofen microsponges. International Journal of Pharmaceutics 2006; 2: 103-17.
- Vyas LK, TaparKK, Laddha BH, Lahoti AO and Nema RK: Formulation and development of anti-blemish preparations using microsponge technology. J Chem Pharm Res 2010; 2: 562-71.
- Panday P, Shukla N, Sisodiya D, Jain V and Mahajan SC: Design and characterization of microsponge loaded controlled release epicutaneous gel of lornoxicam. Appl Med Res 2015; 1: 16-21.
- Jain V and Singh R: Dicyclomine-loaded Eudragit®-based microsponge with potential for colonic delivery: preparation and characterization. Tropical Journal of Pharmaceutical Research 2010; 1: 67-72.
- Tansel C, Nursin G and Tamer B: Preparation and in-vitro evaluation of modified release ketoprofen microsponge. II Farmaco 2003; 58: 101-06.
- Kumar PM and Ghosh A: Development and evaluation of silver sulfadiazine loaded microsponge based gel for partial thickness (second degree) burn wounds. European Journal of Pharmaceutical Sciences 2017; 96: 243-54.
- Chadha R and Bhandari S: Drug-excipient compatibility screening-role of thermoanalytical and spectroscopic techniques. Journal of Pharmaceutical and Biomedical Analysis 2014; 87: 82-97.
- Collett BM: Scanning electron microscopy: A review and report of research in wood science. Wood and Fiber Science 2007; 2: 113-33.
- Zaefferer S: A critical review of orientation microscopy in SEM and TEM. Crystal Research and Technology 2011; 6: 607-28.
- Freeman T, Brockbank K and Sabathier J: Characterising powder flow properties-the need for a multivariate approach. In EPJ Web of Conferences 2017; 03008: 140.
- Rao G and Goyal A: Development of stability indicating studies for pharmaceutical products: an innovative step. International Journal of Pharmaceutical Chemistry and Analysis 2016; 3: 110-16.
- Pokharana M, Vaishnav R, Goyal A and Shrivastava A: Stability testing guidelines of pharmaceutical products. Journal of Drug Delivery and Therapeutics 2018; 2: 169-75.
- Bothiraja C, Gholap AD, Shaikh KS and Pawar AP: Investigation of ethyl cellulose microsponge gel for topical delivery of eberconazole nitrate for fungal therapy. Therapeutic Delivery 2014; 5: 781-94.
- Kumar PM and Ghosh A: Development and evaluation of metronidazole loaded microsponge based gel for superficial surgical wound infections. Journal of Drug Delivery Science and Technology 2015; 30: 15-29.
- Lakshmi CS and Badarinath AV: An updated review of dissolution apparatus for conventional and novel dosage forms. Int J Pharm Res Rev 2013; 2: 42-53.
- Bruschi ML: Strategies to modify the drug release from pharmaceutical systems. Wood head Publishing, Edition 1, Vol. I, 2015: 208.
- Shaikh HK, Kshirsagar RV and Patil SG: Mathematical models for drug release characterization: a review. World J Pharm Pharm Sci 2015; 4: 324-38.
- Higuchi T: Mechanism of sustained‐action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. Journal of Pharmaceutical Sciences 1963; 12: 1145-49.
- Abdelmalak NS and El-Menshawe SF: A new topical fluconazole microsponge loaded hydrogel: Preparation and characterization. Int J Pharm Pharm Sci 2012; 4: 460-68.
- Kadam VV, Patel VI, Karpe MS and Kadam VJ: Design, development and evaluation of celecoxib-loaded microsponge-based topical gel formulation. Applied Clinical Research, Clinical Trials and Regulatory Affairs 2016; 3: 44-55.
- Shah DK and Agrawal A: Formulation and evaluation of polymeric microsponges of ketoconazole for topical delivery. World J Pharm PharmSci 2016; 5: 939-62.
- Osmani RA, Aloorkar NH, Ingale DJ, Kulkarni PK, Hani U, Bhosale RR and Dev DJ: Microsponges based novel drug delivery system for augmented arthritis therapy. Saudi Pharmaceutical Journal 2015; 5: 562-72.
- Osmani RA, Aloorkar NH, Thaware BU, Kulkarni PK, Moin A, Hani U, Srivastava A and Bhosale RR: Microsponge based drug delivery system for augmented gastroparesis therapy: Formulation development and evaluation. Asian Journal of Pharmaceutical Sciences 2015; 5: 442-51.
- Gupta A, Tiwari G, Tiwari R and Srivastava R: Factorial designed 5-fluorouracil-loaded microsponges and calcium pectinate beads plugged in hydroxypropyl methylcellulose capsules for colorectal cancer. International Journal of Pharmaceutical Investigation 2015; 5: 234.
- Parasuraman S: Toxicological screening. Journal of Pharmacology & Pharmacotherapeutics 2011; 2: 74.
- Patel M, Murugananthan G and Gowda KP: In-vivo animal models in preclinical evaluation of anti-inflammatory activity-a review. Int J Pharm Res Allied Sci 2015; 1: 1-5.
- Verma P, Madhav NS and Gupta V: A review article on pharmaceutical validation and process controls. The Pharma Innovation 2012; 1: 51.
- Jadhav N, Patel V, Mungekar S, Bhamare G, Karpe M and Kadams V: Microsponge delivery system: an updated review, current status and future prospects. Journal of Scientific and Innovative Research 2013; 2: 1097-10.
- Chadawar V and Shaji J: Microsponge delivery system. Current Drug Delivery 2007; 4: 123-29.
- Prasad MS, Ajay M, Babu BN, Prathyusha P, Audinarayana N and Reddy DK: Microsponge drug delivery system: a review. Journal of Pharmacy Research 2011; 4: 1381-84.
- Rosen Y, Gurman P and Elman N: Drug delivery: an integrated clinical and engineering approach. CRC Press, Edition 1, Vol. I, 2017: 602.
How to cite this article:
Tomar N, Pawar N and Bahmani K: Review on microsponge leading microporous particulate technology with controlled release, improve stability to provide optimum skin disorders management environment for therapeutic application. Int J Pharm Sci & Res 2020; 11(11): 5360-75. doi: 10.13040/IJPSR.0975-8232.11(11).5360-75.
All © 2013 are reserved by the International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
N. Tomar, N. Pawar * and K. Bahmani
Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani, Haryana, India.
28 January 2020
29 March 2020
31 March 2020
01 November 2020