Development and Characterization of Lornoxicam loaded microsponge gel for Rheumatoid arthritis

 

Sujata S. Sawant*, Sangram S. Patil, Hemant S. Kandle, Manohar D. Kengar, Ganesh B. Vambhurkar, Mangesh A. Bhutkar

Rajarambapu College of Pharmacy, Kasegaon, Dist – Sangli, Maharashtra, India – 415404.

*Corresponding Author E-mail: sawantsujata5@gmail.com

 

ABSTRACT:

Transdermal delivery, a successful novel approach aimed at achieving systematically active level of drug. The drug lornoxicam is a non-steroidal anti-inflammatory drug bearing analgesic, anti-inflammatory, and antipyretic property. The micro sponge technology used to facilitate the controlled release of active drug into the skin in order to reduce the systematic exposure and minimize local cutaneous reactions of active drugs. The main objective of this work was to design and evaluate the gel formation of microsponge entrapped lornoxicam to increase the effectiveness of the treatment. The microsponges were prepared by quasi emulsion solvent diffusion method. The internal phase consisting eudragit RS-100 dissolved in dichloromethane, drug is slowly added to polymer solution with continuous stirring for 4 h, and then mixture was filtered to separate the microsponges. Microsponges was characterized by parameters like scanning electron microscopy, drug content, particle size analysis, compatibility studies using differential scanning calorimetry. Microsponge-loaded gel was characterized by physical parameters of gel, measurement of PH, viscosity study, Drug content study, in-vitro release studies using Franz diffusion cell, cellophane membrane. The prepared gel were subjected to different kinetics models showed that the release data, rheological study, thixotrophy analysis, FT-IR spectral analysis. The release profile of the lornoxicam in the form of microsponges gel was compared with that of pure lornoxicam gel. From the results it can be concluded that microsponges gel LMSG-2 formulation shows drug release in a controlled manner could sustain the drug release over period of 8 hours.

 

KEYWORDS: Piroxicam, Microsponge, Eudragit RS100, Loading efficiency, Crospovidone.

 

 


INTRODUCTION:

Micro sponge delivery system (MDS) is highly cross linked, patented, porous, polymeric microspheres which consists of micro porous beads normally 20-200 microns in diameter 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., that are mostly used for prolonged topical administration[1]

 

The development of an ER micro sponge gel formulation of a drug is to enhance its therapeutic benefits and minimize its side effects, while improving the management of the disease condition[2][3] Thus, control release microsponges delivery systems to maximize the period of time that an active ingredient on the skin surface or within the epidermis while minimizing its transdermal penetration into the body[4]. Microsponges consist of non-collapsible structures with porous surface through which active ingredients are released in controlled manner. When applied to the skin, the microsponge drug delivery system (MDS) releases its active ingredient on a time mode and also in response to other stimuli such as rubbing, temperature, and pH[5] It is a unique technology for the controlled release of topical agents and consists of microporous beads. Delivery system comprised of a polymeric bead having network of pores with an active ingredient held within is developed to provide controlled release of the active ingredients whose final target is skin itself[6] Microsponges are prepared by several methods utilizing emulsion systems as well as by suspension polymerization in a liquid- liquid system. The most common emulsion system used is oil in water with the microsponges being produced by the emulsion solvent diffusion method[7] 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. Moreover, they enhance stability, reduce side effects and modify drug release[8][9] Lornoxicam is used for the treatment of various types of pain, especially of the joints, osteoarthritis, and sciatica. It associated with various side effects including Salicylate sensitivity, gastrointestinal bleeding, and liver or kidney function after oral administration.[10][11][12][13][14][15] Microsponge can entrap a wide variety of substances and can be incorporated into different semisolid and solid dosage forms. The outer surface of microsponge is usually porous, allowing sustained release of substances.[16][17][18][19]

 

MATERIALS AND METHODS:

Lornoxicam was supplied by Naprod life sciences Pvt. Ltd thane Mumbai, Eudragit RS100 was obtained from Evonic Degussa India Pvt. Ltd Mumbai, India. Triethyl Citrate, Di-sodium hydrogen phosphate, Dichloromethane was procured from Merck Specialties Pvt. Ltd. Mumbai, India. Propylene glycol, Orthophosphoric Acid, Carbopol 940, Potassium dihydrogen phosphate was obtained from Loba Chemie Pvt. Ltd., Mumbai, India. Polyvinyl Alcohol was obtained from Aldrich Chemistry, Gmbh Germany. All solvent used were of analytical grade.

 

Methods:

lornoxicam microsponges were prepared by quasi-emulsion solvent diffusion method using Eudragit RS100 with different drug-polymer ratios, three different types of inner phase solvent were used, along with various volumes of the selected organic solvent, the prepared formulas were examined for it its production yield, loading efficiency, particle size and in vitro drug release for formulas have excellent physical properties. Optimum formula that had fast release profile was further fabricated into a tablet using direct compression method, two types of disintegrants along with two different amounts were used, and also the addition of microcrystalline cellulose was examined.

 

Microsponges were prepared by quasi emulsion solvent diffusion technique, using the different concentration of polymer, which requires two immiscible phases internal and external phase with a surfactant. Other factors related to the formulation process, like inner phase and outer phase solvent and its amount, stirring time, stirring speed required for the diffusion and drying (Cevher, et al, 2006).

 

Characterization of pure drug:

Melting point:

Melting point of lornoxicam was pragmatic in range of 2230C-227 0C (literature standard). As experimental values were in good agreement with standard, procured drug was supposed to be pure.

 

UV Analysis:

The spectra of lornoxicam were obtained using a 10µg/ml solution of lornoxicam in 0.1N NaOH, the absorbance maxima was found to be at 380 nm. In dichloromethane the absorbance maxima was found to be at 379 nm. Similarly in phosphate buffer pH 7.4 the absorbance maxima was found to be at 380nm as shown in figure 1, 2 and 3 respectively and absorbance maxima are given in table 1.

 


Figure 1: UV absorption spectrum of lornoxicam in 0.1N NaOH

 

Figure 2: UV absorption spectrum of lornoxicam in dichloromethane

 

Figure 3: UV absorption spectrum of lornoxicam in Phosphate buffer pH 7.4

 

Figure 4: FTIR spectrum of lornoxicam

 


Table 1: Wavelength of maximum absorption (λ max)

Medium

λ max

0.1 N NaOH

380

Dichloromethane

379

Phosphate buffer pH 7.4

380

 

FT-IR Spectra:

The Infrared spectrum of Lornoxicam was obtained using Jasco-4100, Japan, and spectrophotometer. The spectrum shows all prominent peaks of Lornoxicam. The FT-IR spectrum of Lornoxicam is shown in fig.7.4. The spectrum of pure Lornoxicam shows characteristic peaks at 586 cm–1(C-Cl stretch); 1238 cm–1(C=S stretch sulphur compound); 1035 cm–1(S=0strech); 1646 cm–1 (C=N stretch) and 1639 cm–1 (C=O stretch). Comparison between the reported peaks and the observed peaks is shown in table 7.2 Principle peaks were found in the range corresponding to functional group. Appearance of the principle peak in spectrum confirms that the sample is Lornoxicam. FTIR studies revealed that the fundamental peaks of the Lornoxicam are retained in the physical mixture shown in fig.7.5 Results showed that there exist no chemical interaction between Lornoxicam and polymers used in the formulation hence these can be used in the formulation of microsponges.

 

 

 

 

Table 2: Major observed IR peaks of lornoxicam

Functional group

Reported peak (cm-1)

Observed peak (cm-1)

C- Cl (Stretching)

760-540

586

C=S Stretching sulphur compound

1270-1190

1238

S=O stretching

1070-1035

1035

C=N Stretching α ,β-Unsaturated alkyl

1660-1590

1646

C= O Stretching amide

1650

1639

CH3 – CO-

3000-2900

2924

CH3 – N-

1440-1410

1426

 


 

 

Figure 5: FTIR spectra Lornoxicam

 

Figure 6: FTIR spectra Eudragit RS 100

 

Figure 7: FTIR spectra polyvinyl alcohol

 

Figure 8: FTIR spectra physical mixture


Calibration curve:

UV absorption spectrum showed λ max at 380nm. The graph of absorbance Vs concentration for pure lornoxicam was found to be linear in the concentration range of 10-100µg/ml. In 0.1N NaOH, Dichloromethane, Phosphate Buffer pH 7.4. given in fig. 7.6, 7.7, 7.8. Various constants given in table 7.3. Calibration curve for the estimation of Lornoxicam was constructed in 0.1N NaOH, Dichloromethane and 7.4 pH buffer the method obeyed Beer’s Lambert law in the range of 10-100µg/ml, shows linearity and range of lornoxicam concentration.

 

Figure 9: Calibration curve of lornoxicam in 0.1N NaoH

 

Figure 10: Calibration curve of lornoxicam in Dichloromethane

 

Figure 10: Calibration curve of lornoxicam in phosphate buffer pH 7.4

 

Table 3: Various constants for calibration curves

Parameter

Slope

Intercept

R2

0.1N NaOH

0.0358

0.0359

0.9992

Dichloromethane

0.0033

0.0085

0.9946

Phosphate buffer pH 7.4

0.0266

0.0397

0.9989

 

Solubility Study:

Solubility study of lornoxicam were studied in different solvent, the result of lornoxicam solubility in various solvents is shown in table 7.4. Thus 0.1N NaOH and phosphate buffer pH 7.4 for increasing solubility of lornoxicam. However, phosphate buffer pH 7.4 was suitable for drug release and solubility studies.

 

 

 

Table 4: Solubility of lornoxicam in different solvent

Solvent

Solubility (mg/ mL)

UV absorbance

Methanol

6 mg/ml

0.0872

0.1N NaoH

10 mg/ml

1.7655

Distilled water

6 mg/ml

0.0939

0.1N HCL

4 mg/ml

0.0987

Phosphate buffer pH 7.4

8 mg/ml

1.4857

Acetone

4 mg/ml

0.0682

Chloroform

7 mg/ml

1.3219

 

 

 

CHARACTERIZATION OF MICROSPONGES:

Physical Appearance:

The microsponges of lornoxicam prepared by quasi emulsion solvent diffusion technique, microsponges were found to be free flowing small spherical round shaped granules. Microsponges were found to be individual particle of microsponges and small in sizes.

 

Determination of Production Yield:

The microsponges preparation production yields of the batches are ranging from 54.78 to 83.55 as shown in the table 7.5.and graphical presentation shown in fig. 7.9  Thus, for out of all the batches of lornoxicam microsponges (LMS-7) was found to be higher production yield.  The production yield of microsponges decreased due to the increasing concentration of Eudragit RS-100 and dichloromethane. Thus it was observed that the dichloromethane increases, production yield of Microsponges decreases or its vice-versa.


 

Figure 11: Graphical presentation production yield of microsponge’s formulation


Table 5: Production yield of microsponges batches

Batch code

Production yield* (%)

LMS-1

74.15±1.31

LMS -2

70.72±0.58

LMS -3

66.53±0.58

LMS -4

68.55±0.53

LMS -5

64.55±1.20

LMS -6

62.55±1.54

LMS -7

88.57±0.799

LMS -8

81.57±0.27

LMS -9

57.14 ±0.47

 

Actual Drug Content and Encapsulation Efficiency:

Drug content and encapsulation efficiency of microsponges formulation as shown in the table 7.6, it was found that with increasing the amount of polymer, the actual drug content of microsponges decreased the drug content was found to be in range from 54.48 to 83.55%. Drug content was found to 83.55% LMS7 of optimised batch. The encapsulation efficiency was found to be range from 65.73% to 95.04% higher in all formulations. It was observed that the actual drug content and encapsulation efficiency depends on the concentration of polymer, inner solvent, stirring rate, and concentration of outer phase solvent in the formulation. On the basis of high production yield, actual drug content and encapsulation efficiency of microsponges formulation shown that the method was suitable for the preparation of microsponges. Effect of drying on microsponges batches was required 12hr & 24hr but more than 12hr drying effect on production yield of microsponges. The method was shown better result. These results were in accordance with the previous literatures (Jain, et al, 2010)

 

Table 6: Actual drug content and encapsulation efficiency of Microsponges

Batch

Code

Actual drug

Content*(%)

Theoretical drug

Content (%)

Encapsulation

Efficiency* (%)

LMS- 1

63.81±0.13

75

85.33±0.34

LMS -2

61.34±0.22

75

81.33±0.34

LMS -3

58.43±0.29

75

77.90±0.65

LMS -4

60.41±0.56

83.33

72.49±0.87

LMS -5

58.04±0.43

83.33

69.65±0.56

LMS -6

54.78±0.76

83.33

65.73±0.35

LMS -7

83.55±0.65

87.5

95.04±0.42

LMS -8

78.23±0.21

87.5

89.40±0.54

LMS-9

69.34±0.45

87.5

79.24±0..87

 

CONCLUSION:

Microsponge may represent a promising way to increase the dissolution rate of poorly water-soluble drug.

 

ACKNOWLEDGEMENT:

Authors are highly Acknowledge the help of teaching staff of Rajarambapu College of Pharmacy, Kasegaon. For providing necessary information required for research work. Also we are highly Acknowledge the help and guidance of Dr M. M. Nitalikar.

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Received on 16.08.2018            Accepted on 14.10.2018           

© Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech.  2019; 9(3):173-178.

DOI: 10.5958/2231-5713.2019.00029.1