Haola Andani.pdf

International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.3, No.4, pp 2215-2221, Oct-Dec 2011

Formulation and Evaluation of Fluconazole Soap Strips for Dermal infections Swati Jagdale*, Dhaval Bhavsar, Mahesh Gattani, Swapnil Borse, Aniruddha Chabukswar MAEER’s Maharashtra Institute of Pharmacy, S.No. 124,MIT Campus, Paud Road, Kothrud, Pune-411038, MS, India

*Corres. Author: [email protected] Tel. No. +91 9881478118.

Abstract: In present study, antifungal paper soap strips of fluconazole were prepared & evaluated for dermal infections because the presence of thick foam on the infected part causes hydration of stratum corneum for better penetration of drug. The formulation and evaluation of medicated soap strips were carried out in two phases. Phase-I studies optimization, which was carried out to study water absorption capacity using different types of papers (Whatman filter paper no. 1, 41 and 42, filter paper, bond paper and butter paper) by determining the parameters weight gain, size, shape and foam test. From these parameters best soap, concentration of liquid soap solution and papers were selected. Phase-II studies involve incorporation of drug in best soap solution and papers chosen from phase-I studies. The medicated soap strips were prepared by dipping the selected paper in drug containing soap solution. The prepared medicated paper soap strips were characterized for weight gain, foam test, drug content uniformity, FTIR, in vitro drug release studies using diffusion cell with hydrated cellophane membrane and primary skin irritation test. The microbial studies indicate drug activity by zone of inhibition against microorganisms C.albicans, S.typhi, S.aureus, E.coli, klibsiella, B.subtilis, P.aeroginosa, A.niger and A.fumigatus species. The obtained results for prepared medicated soap strip of fluconazole indicate that these strips are economic, convenient, gives good foam on application, uniform in drug content and not showing any skin irritation. Keywords: - Dermal infections, fluconazole, thick foam, hydration of stratum corneum, medicated paper soap strips.

INTRODUCTION Fluconazole is an antifungal azole. It is a broad spectrum antifungal, first approved in Europe in 1988 and then in America in 1990. It was the first single dose treatment approved for vaginal candidiasis. Fluconazole is an effective agent in the treatment and prophylaxis of Candidal infection1-4.Presence of thick foam on the infected part causes hydration of stratum

corneum for better penetration of drug5-9. Topical drug delivery systems are available including medicated soaps having disadvantages like their economy, wastage, no accurate dosage, no proper foam formation etc. Hence the aim for present work was to prepare medicated soap strips which will be more effective against dermal infections.

Swati Jagdale et al /Int.J. PharmTech Res.2011,3(4)

MATERIALS AND METHODS Materials Fluconazole was obtained from Nicholas Piramal as a gift sample. Soap X & soap Y were purchased from local market. Filter paper & Whatman filter paper no. 1, 41 & 42 were from New Neeta chemicals. Butter paper & bond paper were purchased from local market. Methods 1. PHASE-I Selection of soap solution Two non-medicated soaps of different brands were selected and coded as X and Y. Soap solution of varied concentration (5, 10, 15, 20% w/v) were prepared. Formation of foam was avoided during solution preparation. Foam test was the criteria for selection of good soap. The soap capable of producing maximum foam was selected. Selection of paper Six different branded papers (Whatman filter paper no. 1, 41 and 42, filter paper, bond paper and butter paper) were selected and coded as A, B, C, D, E, and F. They were evaluated for their absorption capacity and weight gain. The paper showing maximum absorbing capacity was considered as the best paper. Formation of non medicated paper soap strips The paper soap strips were prepared by Dipping technique using modified disintegration apparatus and air dried overnight at 37±2°C. For this purpose different papers were dipped one after another into the soap solution of varied concentration (5, 10, 15, 20% w/v) and air dried overnight. Evaluation of non-medicated paper soap strips The prepared strips were subjected for determination of size, shape, weight variation, pH and foam test by a reported standard method and an average of 20 strips was taken. 2. PHASE-II Formulation of medicated paper soap strips The drug was incorporated in the selected formulation which showed good absorption capacity in phase-I studies. Accurately weighed drug (2% fluconazole) was mixed with 15% soap powder and distilled water was added under constant and continuous stirring until

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a uniform soap-drug solution was formed. Then paper soap strips were prepared. Evaluation of paper soap strips These prepared medicated soap strips were evaluated for weight gain, foam test, pH, in vitro drug release and primary skin irritation test. Microbial studies have been done by using microorganisms like C.albicans, S.typhi, S.aureus, E.coli, K.pneumoniae, P.aeroginosa, B.subtilis and A.niger species. The % drug content is measured by using UV spectroscopy at λmax 278 nm. In vitro drug release9-12 In vitro drug release of fluconazole from prepared soap strips was studied by using Keshary-Chien diffusion cell. Prehydrated Cellophane paper was used as a membrane in this study. The study was done by using 0.1 N HCl media. The samples were collected at the interval of 3 minutes for a period of 15 minutes. The drug content was estimated by measuring the absorbance at 278 nm. % Drug content The % drug content is measured by using UV spectroscopy at λmax 278 nm. Primary skin irritation test For this, three human volunteers were selected and the prepared soap strips were given to them and checked for irritation. Microbial study13 Microbial study has been done using microorganisms such as C.albicans, S.typhi, S.aureus, E.coli, klibsiella, B.subtilis, P.aeroginosa, A.niger and A.fumigatus species. For measuring the effectiveness of an antimicrobial agent against fungi/bacteria grown in culture, the microorganism of interest was swabbed uniformly across a culture plate. Then a soap strip of 5×5 mm was placed on the surface of the agar. Then the plates were placed in incubator for 24 hrs at 30˚C.The drug diffuses out from the paper soap strip into the agar. The concentration of the compound will be higher next to the strip, and will decrease gradually as distance from the strip increases. IR spectral analysis for drug-excipient intraction14 The studies were carried out using IR method with the help of IR (Varian) spectrophotometer.

Swati Jagdale et al /Int.J. PharmTech Res.2011,3(4)

Table 1: Formulation of fluconazole soap strips Sr. Ingredients Quantity taken No. 1

Soap Y

15 gm each

2

Fluconazole

2 gm

3

Distilled water

100 ml

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Table 2: Evaluation parameters of miconazole soap strips Sr. Parameters 2% Miconazole No. soap strips 1. Weight variation 0.1 ± 0.01 gm 2. Foam height 17 ± 0.02 ml 3. % drug content 96 ± 5.0 % 4. pH 7.0

Table 3: Zone of inhibition obtained in microbial studies Sr. Micro-organism Diameter of Zone of inhibition(cm) No. Strip A Strip B Strip F 1 2 3 4 5 6 7 8 9

A.niger A.fumigatus C.albicans B.subtilus S.typhi E.coli S.aureus P.klebsiella B.aureginosa

2.9 ± 0.1 2.5 ± 0.2 3.3 ± 0.2 3.8 ± 0.3 2.1 ± 0.3 1.8 ± 0.1 4.0 ± 0.4 2.1 ± 0.2 2.3 ± 0.1

2.6 ± 0.2 3.3 ± .02 3.5 ± 0.3 3.9 ± 0.3 1.9 ± 0.4 2.4 ± 0.1 3.6 ± 0.4 2.6 ± 0.2 2.1 ± 0.2

Figure 1: Foam height produced by different nonmedicated paper soap strips.

0.0 ± 0.2 1.4 ± 0.1 1.1 ± 0.2 0.4 ± 0.1 0.8 ± 0.1 0.8 ± 0.1 0.0 ± 0.1 1.5 ± 0.1 0.6 ± 0.1 Figure 2: Weight gain of different non-medicated paper

FOAM TEST

WEIGHT GAIN 0.12

14

0.1

(g)

12

0.08

gain

hight

(ml)

16

10

X

Y

weig ht

X

8

Foa m

6

0.06

Y

0.04

4 2 0

0.02 0

A B C D E FA B C D E F 5%

10%

A B C D E FA B C DE F

A B C D E F 15%

Figure 3: In vitro drug release study of fluconazole soap strips.

5%

10%

A B C D E F 15%

Swati Jagdale et al /Int.J. PharmTech Res.2011,3(4)

Figure 4: Zone of inhibition against various micro-organisms

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Swati Jagdale et al /Int.J. PharmTech Res.2011,3(4)

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Figure 5: IR spectral analysis of fluconazole

Figure 6: IR spectral analysis of soap

soap 100

2355.375 471.513

% T rans m itta nc e

95

1040.990 10.016

1917.761 68.945

490.224 0.00

3499.620 747.062 90

2114.819 -0.049

85 2497.978 847.029

1190.906 660.797

610.454 0.000

1678.997 353.533

80

75

2920.867 191.828

883.109 185.655 1460.319 1926.331

3800

3600

3400

3200 3000

2800

2600

2400

2200 2000 1800 Wavenumber

1600

1400 1200

1000

800

600

400

Swati Jagdale et al /Int.J. PharmTech Res.2011,3(4)

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Figure 7: IR spectral analysis of mixture of fluconazole and soap

100

fluco.+soap

2116.789 0.000

3463.244 0.000 95

2533.298 4.492

1925.869 89.493

% T ra ns m ittan c e

90

1006.386 74.469

85

1244.528 0.000

570.295 13.532

80 3381.928 0.000 75

2717.585 130.139

2356.061 649.346

70 3063.508 632.904

65

612.092 0.000 1699.028 650.741 874.711 0.000

2931.911 520.877

60

1606.910 398.080 1504.239 357.681 1140.924 58.428

3800

3600

3400

3200 3000

2800

2600 2400 2200 2000 Wavenumber

RESULTS AND DISCUSSION 1. Non medicated soap strips From the several papers studied the papers coded A, B and F found to have optimum absorption capacity. The solution of 15% Y soap was found good. All the strips have pH near about 7.0. 2. Medicated soap strips The medicated soap strips found uniform in drug content, weight variation was found to be in the range and foam produced was ranging from 15 to 18 ml. The 15% soap solutions gave best results for foam, weight gain, pH and uniformity of soap distribution as shown in figure 1 and 2. In vitro drug release In vitro drug release studies show the 100% drug released within 10 minutes as shown in figure 3. Primary skin irritation test Primary skin irritation test showed none of the medicated soap strip produces irritation.

1800

1600

1400 1200

81000

600

400

Microbial study Microbial study has been done using microorganisms such as C.albicans, S.typhi, S.aureus, E.coli, klibsiella, B.subtilis, P.aeroginosa, A.niger and A.fumigatus species. It gave zone of inhibition against all of the microorganisms. The diameters of zone of inhibition obtained in microbial testing by different strips against various micro-organisms are given in table 3. IR spectral analysis for drug-excipient interaction The unsubstituted peaks in IR spectra indicate that there is no interaction between drug and soap. CONCLUSION: From the prepared medicated soap strips, the strips of paper encoded B (Whatman filter paper no. 41) shows the best results as compared to other selected papers. The medicated soap strips show excellent release within 10 minutes indicating good efficiency and penetration. The prepared medicated soap strips are convenient to use and new type of dosage form for dermal infections such as candidiasis, aspergillus. It is useful the patients of all ages and sex.

Swati Jagdale et al /Int.J. PharmTech Res.2011,3(4)

9) Rao KP, Patil AB, Reddy H, Sagre P. “Design of

REFERENCES

1) Beale JM, Block JH. “Wilson and Gisvold’s

2) 3) 4) 5) 6) 7)

8)

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Textbook of organic, medicinal and pharmaceutical chemistry”, Wolters Kluwer (India) Pvt. Ltd: New Delhi, 12th ed., 2011; pp:203. Tripathi KD. “Essentials of medical pharmacology”, Jaypee Brothers Medical Publishers: New Delhi, 6th ed., 2008; pp:763. Barar FSK. “Essentials of Pharmacotherapeutics”, S. Chand and company Ltd: New Delhi, 5th ed., 2009; pp:505. http://en.wikipedia.org/wiki/fluconazole. Banker GS, Rhodes CT. “Modern Pharmaceutics”, Marcel Dekker Inc: New York, 4th ed., 2002; pp:190. Montagna W. “The structure and function of skin”, Academic Press: New York, 3rd ed., 1974; pp:10. Misra AN. Transdermal Drug Delivery In: Jain NK editors. “Controlled and novel drug delivery”, CBS publishers and Distributors: New Delhi, 1st ed., 1997; pp:100-127. Indian Standard “Shampoo, Soap basedspecification” (first revision). IS7669-1990: Bureau of Indian standards.1996; NO-AnnexaB2; pp:2-4.

*****

ketoconazole soap strips for dermal infections”, The Pharma Review, 2008; 133-136. 10) Carr MM, Pryce DM, Ive FA. “Treatment of seborrhoeic dermatitis with ketoconazole: Response of seborrhoeic dermatitis of scalp to topical ketoconazole”, Br J Dermatol., 1987; 116; 2: 213-16. 11) Farr PM, Shuster S. “Treatment of seborrhoeic dermatitis with topical ketoconazole”, Lancet., 1984; 2: 1271-72. 12) Green CA, Farr PM, Shuster S. “Treatment of seborrhoeic dermatitis of the face, scalp and trunk to topical ketoconazole Response of seborrhoeic dermatitis of the face, scalp and trunk to topical ketoconazole”, Br J Dermatol., 1987; 116: 217-21. 13) Kokare CR. “Pharmaceutical microbiology principles and applications”, Nirali Prakashan; Pune, 2008; pp:19.4-19.5. 14) Indian Pharmacopoeia, Controller Publications: Delhi, vol. І, 2010; pp:333.

Formulasi dan Evaluasi Strip Sabun Flukonazol untuk infeksi Dermal

1.

Abstrak: Dalam penelitian ini, strip sabun antijamur flukonazol disiapkan & dievaluasi untuk dermal infeksi karena keberadaan busa tebal pada bagian yang terinfeksi menyebabkan hidrasi stratum korneum menjadi lebih baik penetrasi obat. Formulasi dan evaluasi sabun strip obat dilakukan dalam dua fase.Tahap-I studi optimasi, yang dilakukan untuk mempelajari kapasitas penyerapan air menggunakan berbagai jenis kertas (kertas saring Whatman no. 1, 41 dan 42, kertas saring, kertas bond dan kertas mentega) dengan menentukan parameter penambahan berat badan, ukuran, bentuk dan uji busa. Dari parameter tersebut sabun terbaik, konsentrasi sabun cair solusi dan makalah dipilih. Studi fase-II melibatkan penggabungan obat dalam larutan sabun dan kertas terbaik dipilih dari studi fase-I. Strip sabun obat disiapkan dengan mencelupkan kertas yang dipilih dalam obat mengandung larutan sabun. Strip sabun kertas obat yang disiapkan dicirikan untuk penambahan berat badan, tes busa, keseragaman kandungan obat, FTIR, penelitian pelepasan obat in vitro menggunakan sel difusi dengan plastik terhidrasi membran dan uji iritasi kulit primer. Studi mikroba menunjukkan aktivitas obat berdasarkan zona inhibisi terhadap mikroorganisme C.albicans, S.typhi, S.aureus, E.coli, klibsiella, B.subtilis, P.aeroginosa, A.niger dan A.fumigatusspecies. Hasil yang diperoleh untuk strip sabun obat flukonazol yang disiapkan menunjukkan bahwa strip ini ekonomis, nyaman, memberikan busa yang baik pada aplikasi, seragam dalam kandungan obat dan tidak menampilkan kulit apa pun gangguan.

2.

Alat dan bahan : Alat : a.

Spektroskopi UV

b.

Kertas saring

c.

kertas saring Whatman no. 1, 41 & 42

d.

Kertas mentega

e.

kertas bond

Bahan :

3.

a.

Flukonazol

b.

Sabun X

c.

Sabun Y

Metode 1.

fase-I a.

Pemilihan larutan sabun Dua sabun non-medicated dari berbagai merek dipilih dan dikodekan sebagai X dan Y. Solusi Sabun konsentrasi bervariasi (5, 10, 15, 20% b / v) disiapkan. Pembentukan busa dihindari selama persiapan solusi. Tes busa adalah kriteria untuk pemilihan sabun yang baik. Sabun yang mampu menghasilkan busa maksimal dipilih.

b.

Pemilihan kertas

Enam kertas bermerek yang berbeda (kertas saring Whatman no. 1, 41 dan 42, kertas saring, kertas bond dan kertas mentega) dipilih dan dikodekan sebagai A, B, C, D, E, dan F. Mereka dievaluasi untuk kapasitas penyerapan mereka dan penambahan berat badan. Kertas yang menunjukkan daya serap maksimum dianggap sebagai kertas terbaik. c.

Pembentukan strip sabun kertas non obat Strip sabun kertas disiapkan dengan teknik Pencelupan menggunakan alat disintegrasi yang dimodifikasi dan udara kering semalam pada 37 ± 2 ° C. Untuk tujuan ini kertas yang berbeda dicelupkan satu demi satu ke dalam larutan sabun dengan konsentrasi bervariasi (5, 10, 15, 20% b / v) dan udara kering semalam.

d.

Evaluasi strip sabun kertas non-obat Strip yang disiapkan menjadi sasaran untuk penentuan ukuran, bentuk, variasi berat, pH dan uji busa dengan metode standar yang dilaporkan dan rata-rata 20 strip diambil.

2.

fase-II Formulasi strip sabun kertas obat. Obat itu dimasukkan dalam formulasi yang dipilih yang menunjukkan kapasitas penyerapan yang baik dalam studi fase-I. Obat yang ditimbang secara akurat (2% flukonazol) dicampur dengan 15% bubuk sabun dan air suling ditambahkan di bawah pengadukan konstan dan kontinu sampai larutan sabun-obat yang seragam dibentuk. Kemudian strip sabun kertas disiapkan. a.

Evaluasi strip sabun kertas Ini strip sabun obat disiapkan dievaluasi untuk kenaikan berat badan, tes busa, pH, pelepasan obat in vitro dan uji iritasi kulit primer. Studi mikroba telah dilakukan dengan menggunakan

mikroorganisme

seperti

C.albicans,

S.typhi,

S.aureus,

E.coli,

K.pneumoniae, P.aeroginosa, B.subtilis dan A.niger spesies. Isi obat% diukur dengan menggunakan spektroskopi UV pada λmax 278 nm. b.

Rilis obat in vitro9-12 Pelepasan obat flukonazol secara in vitro dari strip sabun yang disiapkan dipelajari dengan menggunakan sel difusi Keshary-Chien. Kertas Cellophane prahidrasi digunakan sebagai membran dalam penelitian ini. Penelitian dilakukan dengan menggunakan 0,1 N HCl media. Sampel dikumpulkan pada interval 3 menit untuk jangka waktu 15 menit. Kandungan obat diperkirakan dengan mengukur absorbansi pada 278 nm.

c.

% Konten obat Isi obat% diukur dengan menggunakan spektroskopi UV pada λmax 278 nm.

d.

Tes iritasi kulit primer Untuk ini, tiga sukarelawan manusia dipilih dan strip sabun disiapkan diberikan kepada mereka dan diperiksa untuk iritasi.

e.

Studi mikro13 Studi mikroba telah dilakukan menggunakan mikroorganisme seperti C.albicans, S.typhi, S.aureus, E.coli, klibsiella, B.subtilis, P.aeroginosa, A.niger dan A.fumigatus

spesies. Untuk mengukur efektivitas agen antimikroba terhadap jamur / bakteri yang ditanam dalam kultur, mikroorganisme yang tertarik diseka secara seragam di seluruh lempeng budaya. Kemudian strip sabun 5 × 5 mm ditempatkan pada permukaan agaragar. Kemudian piring ditempatkan dalam inkubator selama 24 jam pada 30˚C. Obat berdifusi keluar dari strip sabun kertas ke dalam agar. Konsentrasi senyawa akan lebih tinggi di sebelah strip, dan akan berkurang secara bertahap saat jarak dari strip meningkat. f.

IR spektral analisis untuk obat-excipient intraction14 Studi dilakukan menggunakan metode IR dengan bantuan spektrofotometer IR (Varian).

4.

Evaluasi a. Kenaikan berat badan b. Uji ph c. Tes busa d. Pelepasan obat in vitro dan e. Uji iritasi kulit primer

5.

6.

Formulasi Sabun Y

15 gram

Sabun X

15 gram

Fluconazole

2 gm

Air suling

100 ml

Hasil dan pembahasan 1. strip sabun Non obat Dari beberapa makalah yang dikaji makalah yang diberi kode A, B dan F ditemukan memiliki kapasitas penyerapan yang optimal. Solusi dari 15% sabun Y ditemukan baik. Semua strip memiliki pH sekitar 7,0. 2. Strip sabun obat Strip sabun obat ditemukan seragam dalam kandungan obat, variasi berat ditemukan berada di kisaran dan busa yang dihasilkan berkisar 15-18 ml. Larutan sabun 15% memberikan hasil terbaik untuk busa, berat badan, pH dan keseragaman distribusi sabun seperti yang ditunjukkan pada gambar 1 dan 2.

a. Pelepasan obat in vitro Studi rilis obat in vitro menunjukkan obat 100% dilepaskan dalam 10 menit seperti yang ditunjukkan pada gambar 3. b. Tes iritasi kulit primer

Uji iritasi kulit primer menunjukkan tidak ada sabun yang menghasilkan iritasi. c. Studi mikroba Studi mikroba telah dilakukan menggunakan mikroorganisme seperti C.albicans, S.typhi, S.aureus, E.coli, klibsiella, B.subtilis, P.aeroginosa, A.niger dan A.fumigatus spesies. Ini memberi zona penghambatan terhadap semua mikroorganisme. Diameter zona inhibisi yang diperoleh dalam pengujian mikroba oleh strip yang berbeda terhadap berbagai mikro-organisme diberikan dalam tabel 3. d. Analisis spektral IR untuk interaksi eksipien. Puncak yang tidak disubstitusi dalam spektrum IR menunjukkan bahwa tidak ada interaksi antara obat dan sabun.

7.

Kesimpulan Dari strip sabun obat yang disiapkan, potongan kertas yang disandikan B (kertas saring Whatman no. 41) menunjukkan hasil terbaik dibandingkan dengan kertas terpilih lainnya. Strip sabun obat menunjukkan pelepasan yang sangat baik dalam 10 menit menunjukkan efisiensi dan penetrasi yang baik. Strip sabun medicated yang disiapkan mudah digunakan dan jenis sediaan baru untuk infeksi kulit seperti kandidiasis, aspergillus. Ini berguna bagi pasien segala usia dan jenis kelamin.