INTRODUCTION:

Controlled release drug delivery engages drug encapsulating forms that support reducing the active agents in a controlled way for a long time. Such formulations offer numerous superioritiesover traditional drug delivery methods, including drug release rate and increased patient adherence. Microspheres are novel vehicles for many controlled delivery applications because of their Biocompatibility, good bioavailability, and controlled release of drugsinthelonger term.¹

Microspheres contain tiny globular particles that possess dimensions of particle range 0.1-200µm and are combined withbiodegradable and non-biodegradable material. Absorption of drug &adverse drug reaction ascribed to the gastrointestinal tract mucosa is improved for the reason that of tiny particles dimension of microparticle whereby extensively spread all over the gastrointestinal tract.²

Fundamentally, every particle is the blend of active agents diffuse in polymer and drug release patterns. It provides precise transportation of tiny quantities of mighty active agents along with lesser active agent concentration at the area apart from the destination. The management along with previous to show at the area of action by combining the therapeutic agent with transporter molecule, we can modify the nature of therapeutic agents in-vivo. The nature of the transporter molecule would affect the clearance kinetics, metabolism, and intracellular interaction of therapeutic agents. Taking advantage of that modification in pharmacodynamics may change to increase biological action.³

This delivery arrangement of controlled released aims to supply the required quantity of active agents to the targeted area after gaining the optimum therapeutic level, to control the desired concentration of the drug in the area of action.⁴

The work is going on in an attempt to formulate a controlled drug delivery system for Diltiazem Hcl in form of a microsphere. So, by enhancing the time of the release of the drug, the availability can be increased.

ADVANTAGES:^5-6

1. Controlled release microspheres extending the duration of therapeutic effect.

2. Lowers the dosing repetition and enhances patient compliance.

3. Due to their shape & size, they are comfortable to be used in the injection form.

4. Better drug utilizationwill improve bioavailability and less side effects.

5. Allow controlled manner release of the drug.

6. Decreased the possibility of GIT irritation.

7. Can mask the bad odor of drugs.

8. It avoids first-pass metabolism.

DISADVANTAGE:⁷

1. It can vary in controlled release rate because of various factors like the presence of food, rate of transit through GIT, and other intrinsic and extrinsic factors.

2. Chances of differences in release rate from one to another dosage form.

3. Microspherecarriers’ removal is difficult from the body in the case of parental application.

4. Formulation release rate can be modified.

5. Differences in the release pattern may cause high toxicity.

6. These dosage formulations cannot chew or crush.

PATENTS OF MICROSPHERES:^8-14

Sl No.	Patent no.	Drug	Reference no.
1.	CA2579533	Irinotecan	08
2	DE1999609777	Levonorgestrel	09
3	CA2217462	Cyclosporin	10
4	EP19980924438	Cimetidine	11
5	DE1994632867	Doxorubicin	12
6	CN201110142359	Ketoprofen	13
7	US08455091	Ganciclovir	14

CLASSIFICATION OF POLYMERS:

1. NATURAL POLYMERS:

These are the polymers that occur in nature and are existing in natural sources like plants and animals.²

a. Protein:

Example - gelatin.

b. Carbohydrate:

Example - cellulose, cyclodextrin, chitosan, hyaluronic acid, starch.

2. SYNTHETIC POLYMERS:

These are polymers that humans can artificially create in the lab.

a. Biodegradable polymers:¹⁵

Example - Poly-β-hydroxybutyrate co-β-hydroxy valerate (PHBV), polyglycolic acid (PGA), polylactic acid (PLA).

b. Non-biodegradable polymers:

Example - acrolein, polyethylene, Teflon.

3. SEMI-SYNTHETIC POLYMERS:

Obtained by making modifications in natural polymers artificially in the lab. These polymers are prepared by chemical reactions.

Example- cellulose acetate, vulcanized rubber.

IDEAL CHARACTERISTICS OF CARRIERS:¹⁶

i. Gives stability to drug molecule.

ii. It helps sterilizabilityofdrugs.

iii. Helps to protect the drug.

iv. Provide aqueous stability.

TYPES OF MICROSPHERES:

1. Magnetic microsphere:^17-18

This is a very prime delivery system, which helps drugsto reach the diseased site. In place of more quantity of freely circulating drugs can be replaced by a smaller quantity of the magnetically targeted drug. Magnetic carriers get magnetic responses for magnetic fields from the added material that is used for magnetic microspheres like chitosan, dextran, etc. The two types of magnetic microspheres are-

i. Therapeutic magnetic microspheres for delivering chemotherapeutic agents to liver tumors, drugs such as proteins and peptides can be used in these systems.

ii. Diagnostic microspheres-mainly used liver metastases imagining.

2. Radioactive microsphere:

Radioactive microspheres are inserted into the arteries leading to the tumors of interest. So, radioactive microspheres deliver high radiation dosage to the targeted sites without disturbing the normal other tissues. Radioactive microspheres are released within a typical radioisotope distance, and different types of radioactive microspheres are α emitter emitters&γ emitters.¹⁹

3. Floating microspheres:

In this dosage form, the dosage density is less than the gastric fluid, So, it floats in the stomach without affecting GI emptying time. The drug released is prolonged at the desired rate, if the dosage form floats in gastric fluid, it increases gastric residence time and enhancesfluctuation in drug plasma concentration, it reduces the chances of dose dumping and producesa therapeutic effect.^20-21

4. Polymeric microspheres:

Various classes & polymers microspheres can be classified and they are biodegradable polymeric microspheres& synthetic polymeric microspheres,

→Synthetic polymeric microspheres

→Biodegradable polymeric microspheres.

5. Bioadhesive microspheres:

Adhesion can be explained as the sticking ofthe drug to the membrane by using the adhesion property of water-soluble polymer, Adhesionof dry dosageform to membrane such an ocular, rectal, buccal nasal ete. Can be defined as bio adhesion.These microspheres show prolonged residence time at the site of application Cause well in contact with the absorbing area and givea better therapeutic effect.²²

METHODS OF PREPARATION:^23,24,25

1. Single emulsion method:

The natural polymers are liquified or dispersed in the aqueous phase or non-aqueous phase followed by dispersion in non-aqueous medium e.g., oil. Afterward cross-linking of the dispersed globules is done by the chemical cross-linkers glutaraldehyde, teraphthalyl chloride, formaldehyde, etc. So, after centrifugation, separation, and washing the microspheres can be obtained.

2. Double emulsion technique:

In this method, multiple emulsions w/o or o/w is prepared, and the watery protein solution is dispersed in a hydrophobic organic continuous medium. The formed primary emulsion is subjected to homogenization before adding the aqueous phase of polyvinyl alcohol. This results in the formation of multiple emulsions.This emulsion is then subjected to solvent removal or extraction and formed microspheres.

3. Phase Separation Technique:

In this type of technique, the polymer is primarily dissolved in a suitablesolvent and the drug is dispersed by making its aqueous solution. After ward, the phase separation is carried out by the techniques like the addition of incompatible polymer or changing of pH, etc. Result polymer-rich globules are formed which became hardened after some time. On separation, the microspheres are formed and collected.

4. Polymerization Technique:

For this technique, dispersion is made by using active material and the aqueous solution of sodium hydroxide (NaOH) with a surfactant medium. After heating the above mixture polymerization starts which on settling forms microspheres.

5. Solvent Extraction Technique:

The solvent extraction technique depends on the withdrawal of the organic phase by extraction of the organic solvent. The organic solvent used such as isopropyl alcohol and the organic phase is withdrawn by extraction with water. The therapeutic advantage of microencapsulated drugs and vaccines brought forth the need to form such particles in larger quantities and insufficient quality suitable for clinical trials and commercially successful. Our findings will be outlined according to the four major substeps of microsphere formation by solvent extraction/evaporation.

6. Spray Drying and Spray Congealing:

In this type of technique, the polymer is firstly dissolved in a suitable organic solvent like acetone, dichloromethane, etc. Then the drug in the solid form is then dispersed in the polymeric solution. Then this dispersion is atomized in a stream of hot air. As a result, the atomization leads to the formation of the small droplets from which the solvent evaporates continuously leading to the formation of the microsphere.

EVALUATION OF MICROSPHERES:^26-30

1. Percentage (%) yield of microspheres:

Dried microspheres were collected and weighed accurately. The percentage yield can be calculated using the following formula,

Percentage (%) yield = mass of microspheres obtained/(drug+polymer) × 100

2. Analysis of particle size:

Distribution particle size estimation was done by sieving technique. Size distribution plays a major role in estimating the release characteristics of the microspheres.

3. Angle of repose:

Angle of repose was carried out by helping of funnel method for determining flow properties. Microspheres weighed accurately were taken in a funnel and then adjust the height of the funnel in a way that the tip of the funnel just touches the heap of blends. The blends are passed through a funnel freely on the surface. The diameter of the blend cone was measured and the angle of repose was calculated by using this equation:

tanθ = h/r

where θ = angle of repose

h = height of the pile

r = radius of the base

4. Drug content determination:

Weighed accurately 100mg microspheres were crushed in a glass mortar and pestle and powdered microspheres were dissolved in 100ml of a suitable solvent. The solution was filtered and the filtrate was analyzed for drug content at UV- visible spectrophotometer.

5. Swelling studies:

A known amount (50mg) of microspheres were placed in a glass vial containing 10ml of distilled water at 37± 0.50C in an incubator with occasional stirring. The microspheres were periodically removed and blotted with filter paper and their result of changes in weights were measured during the swelling until equilibrium was attained. Finally, the weight of the swollen microspheres was recorded after a specific period of 3 hours, and the swelling ratio (SR) was then determined from the following formula/equation.

SR=(We-Wo) / Wo

Where,

Wo = Initial weight of the dry microspheres,

We = Weight of the swollen microspheres at equilibrium swelling in the media.

6. Encapsulation efficiency:

Encapsulation efficiency was calculated using the following formula/equation;

E = (Qp / Qt) X 100

Where

E = percentage (%) of encapsulation of microspheres,

Qp = quantity of drug encapsulated in microspheres,

Qt = quantity of the drug added for encapsulation.

7. In vitro dissolution studies:

In-vitro Dissolution studies were carried out for the microspheres, employing the USP XXIII apparatus (Basket method) at 37±0.5⁰C rotated at a specific/constant speed of suitable rpm using a suitable dissolution medium. A known sample of microspheres equivalent to 100mg of loaded microspheres was used in each test. The sample was periodically withdrawn at a suitable time interval and the volumes were replaced with fresh dissolution medium/bufferto maintain the sink condition. The sample was analyzed spectrophotometrically at suitable lambda max (nm).

8. Carr’s index:

It was measured by using the following formula/equation,

Carr’s Index = {(Vb –Vt) / Vb} × 100

WhereVb and Vt are the bulk volume and tapped volume.

FACTORS THAT INFLUENCE PROPERTIES OF MICROSPHERES:

1. Polymers are commonly used to form microspheres.

2. Choice of solvent:

· It should be able to dissolve the chosen polymers.

· Should be Poorly soluble in the continuous phase.

· Should have high volatility and a low boiling point.

· Should be Low toxicity.

· Alternative components (Dispersed Phase).

a) Co-Solvent: The organic solvents miscible with water such as ethanol and methanol.

b) Porosity generator: It will increase the degradation rate of polymer and improves drug release rate.

3. Continuous phase:

Surfactant:

· It reduces the surface tension of the continuous phase.

· Avoids the coalescence and agglomeration of drops.

· Stabilizes the emulsion.

APPLICATIONS OF MICROSPHERES:^31,32

The brief outline of various applications of the microsphere is explained as follows

1. Microspheres for Ocular delivery:

The most important applications of drug-loaded ophthalmic delivery systems are for glaucoma therapy, especially cholinergic agonists like pilocarpine. The short elimination half-life of aqueous eye drops can be extended from a very short time (1-3 min) to a prolonged time (15-20min) using microspheres that have biodegradable properties e.g.: Poly alkyl cyanoacrylate.

2. Fluorescent microspheres in imaging:

These are made up of polystyrene or polyvinyl toluene, monodisperse systems ranging in size from 20nm to 4µm. Preparation of fluorescent microspheres comprising, swelling of the polymeric microsphere so, that fluorescent dyes may enter the microsphere pores. Non-swelling the polymeric microspheres so that the fluorescent dyes become physically entrapped in the pores.

3. Microspheres for DNA Delivery:

Microspheres have been newly/ recently used as a delivery vehicle for the transfer of plasmid DNA which leads to improving the transfer of plasmid DNA and their stability in the bio- environment. Truong-Le & Co-workers (1998) developed a novel system for gene delivery based on the use of DNA-gelatin microspheres/ nanoparticles formed by salt-induced complex coacervation of gelatin and plasmid.³⁵

4. Adjuvant effect for vaccines:

An adjuvant effect of the microspheres/nanoparticles with either matrix entrapped or surface adsorbed vaccines have been observed in several studies on substances or oral administration. “Kreuter and Co-workers” observed that Polymethyl methacrylate microspheres consisting of influenza antigen-induced significant antibody response. Oral delivery of antigens with microspheres may be an elegant means of producing an increased/enhanced Immunoglobin A (Ig A) antibody response.^44,46-49

5. Microspheres in chemotherapy:

The most promising/ important application of microspheres is possible to use as carriers for anti-tumor agents. Enhanced/increased endocytic activity and leaky vasculature administrated microspheres. Stealth microspheres are prepared by coating with soluble polyoxyethylene. The accumulation of non-stealth microspheres in the Reticulo Endothelial System (RES) may also be exploited for cancer chemotherapy treatment.^33,34,45

6. Microspheres for Lymph targeting: -

The major purpose/ intention of lymph targeting is to provide effective anticancer chemotherapy to prevent the metastasis of tumor cells by accumulating the drug in the regional lymph node. Example: Poly alkyl cyanoacrylate microspheres bearing anticancer drugs for tumors of the peritoneal cavity. Poly (lactide-co-glycolide) microspheres for the lymphatic diagnostic agents.

Medical application:^36-43

· Microspheres Vaccine delivery for treatment of diseases like hepatitis, influenza, pertussis, ricin toxoid, diphtheria, and birth control.

· Tumor targeting with doxorubicin and treatments like leishmaniasis.

· The release of proteins, hormones, and peptides over an extended period.

· The gene therapy with DNA plasmids and delivery of insulin.

· The magnetic microspheres can be used for stem cell extraction and bone marrow purging.

· Microspheres are used in the isolation of antibodies, cell separation, and toxin extraction by affinity chromatography.

· The Passive targeting of leaky tumor vessels, active targeting of tumor cells, antigens, by intra- arterial/ intravenous application.

· Microspheres are used for various diagnostic tests for infectious diseases like bacterial, viral, and fungal.

CONCLUSION:

The present review article suggests that microspheres are abetter choice of drug delivery system than many other types of drug delivery systems. In the future by combining various other designs andplanning and strategies, microspheres will find a central and significant place in novel drug delivery, particularly in diseased cell sorting, diagnostics, gene and genetic materials, safe, targeted, specific, and effective in-vivo delivery.

REFERENCES:

1. Jha MK: Modified release formulations to achieve the quality target product profile (QTPP). Int.J. Pharm.Sci. Res. 2012; 3(2): 376-86.

2. Prasanth V, Moy V, and Chakraborthy A et al: Microspheres: An overview. Int. J. Pharm. Sci. Res. Biomed. Sci. 2011; 2(3): 32-8.

3. Fu X, Ping Q and Gao Y. Effects of formulation factor on encapsulation efficiency and release behavior in-vitro of huperzine A-PLGA microspheres. J. Microencapsul. 22: 705-14.

4. Ghalop SB, Banerjee SK and Throat RM et al: Hollow microsphere a Review. Int. J. Pharm. Sci. Rev. Res. 2010; 1:10-15.

5. Kavita K, RajeV, et al. Albumin Microspheres: A Unique system as drug delivery carriers for nonsteroidal anti-inflammatory drugs. 2012; 5(2):12

6. Asija R, Sharma D, and Mall KR: Solvent evaporation matrix erosion method: a novel approach for floating microsphere development. Drug Discov. Ther. 2014; 2: 24-9.

7. Kunchu K and Ashwani RV et al: Albumin microspheres: An Unique System as Drug Delivery Carriers for nonsteroidal anti-inflammatory drugs (NSAIDS). Int. J. Pharm. Sci. Rev. Res. 2010; 5:10-17.

8. CA 2579533, Andrew Lennard Lewis Peter William Stratford Maria Victoria Gonzalez-Fajardo Yiqing Tang, Publication: 06-09-05.

9. DE1999609777, S. Adam CANTOR Hye-Ok Choi Joaquin Delgado U. Chan KOThu-Van Tran, Publication: 15-04-04.

10. CA 2217462, Zebunnissa Ramtoola, Publication: 03-08- 10

11. EP20070808011, Hong KeeSah, Publication: 03-04-13

12. DE1994632867, Yan Chen Bruce Nathaniel Gray, Publication: 22-04-04

13. CN 201110142359, Zhu Limin Sciascia Nie Shen Wei, Publication: 28-09-11

14. US08455091, Rocio Herrero-Vanrell Miguel F. Refojo, Publication: 17-02-98

15. Kataria S, Midha A and Sandhu P et al: Microsphere A review. Int. J. Res. Pharm. Chem. 2011; 1:1184-98.

16. Kunchu K and Ashwani RV et al: Albumin microspheres: An Unique System as Drug Delivery Carriers for nonsteroidal anti-inflammatory drugs (NSAIDS). Int. J. Pharm. Sci. Rev. Res. 2010; 5:10-17.

17. Prasanth VV, Moy AC, Mathew ST, Mathapan R, Microspheres: an overview, Int. J. Res. Pharm. Biomed. Sci. 2011; 2(2): 332-8.

18. Boggarapu Prakash Rao, Rashmi Mathews, Karedla Phani Krishna, Beny Baby, and Poornima, Spray-dried gastroretentive floating microparticles: Preparation and in vitro evaluation, Pak. J. Pharm. Sci. 2013;26(4), 707-13.

19. Priya P, Sivabalan M, Balaji M, Rajashree S, Muthu DH, Microparticle: a novel drug delivery system, Int. J. Pharma Bio Sci. 2013; 3(2):310-26.

20. Chitra Singh, Suresh Purohit, Madhu Singh, B.L. Pandey, Design, and Evaluation of microspheres: a review. Journal of Drug Delivery Research. 2013; 2(2): 18-26.

21. Soni LM, Kumar M, Namdeo PK, Sodium alginate Microspheres for extending drug release: formulation and in vitro evaluationInt. J. Drug Deliv. 2010; 2(1):64-8.

22. Ramteke KH, Jadhav VB, Dhole SN, Microspheres: as carriers used for novel drug delivery system. IOSR Journal of Pharmacy. 2012;2(4): 44-8.

23. Bhalerao S.S., Lalla J.K., Rane M.S. A study of electrokinetic and stability property of suspension of diltiazem hydrochloride microcapsule. Indian Drugs. 2001; 38: 464-467.

24. Chowdary K.P., Ramesh K.V. Studies on microencapsulation of diltiazem, J. Pharm. Sci. 1993; 55:52-4.

25. Reddy M.N., Shriwaikar A.A. Rosin. A polymer for microencapsulation of diltiazem hydrochloride for sustained release by emulsion-solvent evaporation technique. Indian J. Pharm. Sci. 2000; 62:308-10.

26. Alexander Florence. Novel oral drug formulations: Their potential in modulating adverse effects. Drug Safety. 1994; 10(3): 233-66.

27. Arshady R. Albumin microsphere and microcapsule; methodology of manufacturing techniques. J Controlled Release. 1990; 111-31.

28. Kim CK, Kim MJ, Oh KH. Preparation and evaluation of sustained-release microspheres of terbutaline sulfate. Int J Pharm. 1994; 213-19.

29. Lorenzo-Lamosa ML. Design of microencapsulated chitosan microspheres for colon drug delivery. J Control Release. 1998; 52(12):109-18.

30. Wan LSC, Heng PWS, Chan W. Surfactant effects on alginate microspheres. Int J Pharm. 1994; 267–75.

31. Kreuter J, Nefzger M, Liehl E, CzokR, Voges R. Microspheres – A Novel Approach in Drug Delivery System. J Pharm Sci. 1983; 72: 1146.

32. Paulo Costa, Jose Manuel Sousa Lobo, Modelling and comparison of dissolution profiles. European Journal of Pharmaceutical Sciences. 2001; 13: 123- 33.

33. Keys, H.M., Bundy, B.N., Stehman, F.B., Muderspach, L.I., Chafe, W.E., Suggs, C.L., Walker, J.L., and Gersell, D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. The New England J of Medicine. 1999; 340: 1154- 61.

34. Nithya Shanthi C, Rakesh Gupta, Arun Kumar Mahato. Traditional and emerging applications of microspheres: A Review. Int. J. Pharm. Tech. Res. 2010; 2(1), 675-81.

35. Soni LM, Kumar M, Namdeo PK. Sodium alginate Microspheres for extending drug release: formulation and in vitro evaluation. International Journal of Drug Delivery. 2010; 2(1):64-8.

36. Pradesh TS, Sunny CM, Varma KH, Ramesh P. Preparation of microstructured by droxyapatite microspheres using oil in water emulsion. Bull Matter. Sci. 2005; 28(5):383-90.

37. Asija Rajesh, Bansal Vishnu, Asija Sangeeta, Rathore Suryabhan Singh. Matrix Tablet: A Promising Tool for Oral Controlled Release Drug Delivery. Asian J. Pharm. Res. 2013; 3(4): 213-9.

38. Atul Bisen, Alok Pal Jain, Suchit Jain. Formulation and Evaluation of Zidovudine Loaded Microsphere. Asian J. Res. Pharm. Sci. 2013; 3(4): 200-5.

39. Pooja M. Nikam, S.B. Gondkar, R.B. Saudagar. Brain Targeting Drug Delivery System: A Review. Asian J. Res. Pharm. Sci. 2015; 5(4): 247-52.

40. Kaustubh V. Gavali, Manohar D. Kengar, Kiran V. Chavan, Vaishnavi P. Anekar, Naziya I. Khan. A Review on Microsphere and it’s Application. Asian J. Pharm. Res. 2019; 9(2): 123-9.

41. Dhadde Gurunath S., Mali Hanmant S., Raut Indrayani D., Nitalikar Manoj M., Bhutkar Mangesh A. A Review on Microspheres: Types, Method of Preparation, Characterization and Application. Asian Journal of Pharmacy and Technology. 2021; 11(2):149-55.

42. Wajid Ahmad, Jaza Quazi, Reshma Khan, Nadeem Ahmad, Nawed Ansari. A Comprehensive Review on Microspheres. Asian J. Pharm. Technol. 2022; 12(2):136-40.

43. Vinod R, Ashok Kumar P, Amit S Yadav, Someshwara Rao B, Suresh V Kulkarni. Formulation and Evaluation of Controlled Release Microspheres of Zidovudine. Research J. Pharma. Dosage Forms and Tech. 2010; 2(1):96-9.

44. Rutuja K. More, Diksha S. Sonawane, Moreshwar P. Patil, Sanjay J. Kshirsagar. Rutuja K. More, Diksha S. Sonawane, Moreshwar P. Patil, Sanjay J. Kshirsagar. Res. J. Pharma. Dosage Forms and Tech. 2018; 10(3): 193-9.

45. Deepak S. Kshirsagar, R. B. Saudagar. Microsphere: A Review. Research J. Topical and Cosmetic Sci. 2016; 7(1): 27-37.

46. Katta. Manogna, E. Nanda Krishna Reddy, T.N. Shilpa. Polymeric Novel Vesicular Drug Delivery System: An Updated Overview of Microspheres. Research J. Topical and Cosmetic Sci. 2017; 8(2): 64-72.

47. VN Deshmukh, JK Jadhav, VJ Masirkar, DM Sakarkar. Formulation, Optimization and Evaluation of Controlled Release Alginate Microspheres Using Synergy Gum Blends. Research J. Pharm. and Tech. 2009; 2(2): 324-7.

48. UK Patil, Ravish Sahu, SK Yadav. Formulation and Evaluation of Controlled Release Microspheres Containing Metformin Hydrochloride. Research J. Pharm. and Tech. 2009; 2(1): 176-9.

49. Ayanam Vasavi, Miriyala Mrunalini, Ayanam Vasanthi, G. Raveendra Babu, M. Sowjanya. Formulation and Evaluation of Sustained Release Stavudine Microspheres by Ionotropic Gelation Method. Asian J. Pharm. Technol. 2022; 12(2):119-24.

50. A Saravanakumar, Sunita Minz, Madhulika Pradhan, Pavani Sure, Atul N Chandu, Umesh Mishra, K Kamalakannan, T Sivakumar.Polylactic Acid Microspheres as A Potential Vaccine Delivery System for the Tetanus Toxoid: Preparation and In Vitro Dissolution Study. Research J. Pharm. and Tech. 2008; 1(4):453-9.

Received on 05.07.2022 Modified on 13.10.2022

Asian J. Pharm. Res. 2023; 13(3):163-168.

DOI: 10.52711/2231-5691.2023.00031