materials and methods

4
MATERIALS AND METHODS Metformin hydrochloride was obtained as a gift sample from Strides Arcolab Ltd., Bangalore. Chitosan was purchased from Sigma Aldrich, Bangalore. HPMC was obtained from Shreeji chemicals, Mumbai, India. Dibutyl phthalate was obtained from SD Fine Chemicals, Mumbai. All other chemicals and reagents used in the study were of analytical grade. Preparation of the Transdermal Patches Matrix type transdermal patches of Metformin HCl were prepared by solvent evaporation technique using different proportions of polymers like Chitosan and HPMC in cylindrical glass mould with open end on both sides. The backing membrane was cast by pouring 5% (w/v) PVA solution on bottom of the mould which was wrapped with aluminum foil followed by drying at 60°C for 6 h in an oven. Requisite ratios of the two polymers were weighed and they were then dissolved in ethanol: dichloromethane (1:1) as a solvent. Dibutyl phthalate (20%) of polymer composition was used as a plasticizer. The drug was added 20% w/w of the total weight of polymer, in the homogeneous dispersion, by slow stirring on a magnetic stirrer. On the PVA backing membrane casted earlier the uniform dispersion (3 ml each) was casted and dried at 40°C for 6 h. After drying patches were removed from the mold, wrapped with aluminium foil and kept in desiccators until they were used for further study. The formulation chart is given in Table 1. Evaluation of Transdermal Patches Drug polymer Interaction Study 7 The physicochemical compatibility between Metformin HCl and polymers used in the films was studied by using Fourier transform-infrared (FT-IR- 8400, Shimadzu Co., Japan) spectroscopy. The pellatization was done by the KBr pellet method. The FT-IR spectra were recorded in the wavelength region between 4000 and 400 cm -1 . The spectra obtained for Metformin HCl and physical mixtures of Metformin HCl with polymers were compared. Differential Scanning Calorimetry

Upload: mia-riswani

Post on 12-Nov-2015

2 views

Category:

Documents


0 download

DESCRIPTION

ytufglufl7ui

TRANSCRIPT

MATERIALS AND METHODS Metformin hydrochloride was obtained as a gift sample from Strides Arcolab Ltd., Bangalore. Chitosan was purchased from Sigma Aldrich, Bangalore. HPMC was obtained from Shreeji chemicals, Mumbai, India. Dibutyl phthalate was obtained from SD Fine Chemicals, Mumbai. All other chemicals and reagents used in the study were of analytical grade. Preparation of the Transdermal PatchesMatrix type transdermal patches of Metformin HCl were prepared by solvent evaporation technique using different proportions of polymers like Chitosan and HPMC in cylindrical glass mould with open end on both sides.The backing membrane was cast by pouring 5% (w/v) PVA solution on bottom of the mould which was wrapped with aluminum foil followed by drying at 60C for 6 h in an oven. Requisite ratios of the two polymers were weighed and they were then dissolved in ethanol: dichloromethane (1:1) as a solvent. Dibutyl phthalate (20%) of polymer composition was used as a plasticizer. The drug was added 20% w/w of the total weight of polymer, in the homogeneous dispersion, by slow stirring on a magnetic stirrer. On the PVA backing membrane casted earlier the uniform dispersion (3 ml each) was casted and dried at 40C for 6 h. After drying patches were removed from the mold, wrapped with aluminium foil and kept in desiccators until they were used for further study. The formulation chart is given in Table 1. Evaluation of Transdermal Patches Drug polymer Interaction Study7The physicochemical compatibility between Metformin HCl and polymers used in the films was studied by using Fourier transform-infrared (FT-IR- 8400, Shimadzu Co., Japan) spectroscopy. The pellatization was done by the KBr pellet method. The FT-IR spectra were recorded in the wavelength region between 4000 and 400 cm -1. The spectra obtained for Metformin HCl and physical mixtures of Metformin HCl with polymers were compared. Differential Scanning Calorimetry About 5 mg of sample was weighed and crimped into an aluminium pan and analysed at scan range from 0 C - 300C at the heating rate of 5C/min under nitrogen flow of 25ml/min. Scanning electron microscopy Morphological details of the transdermal patches after swelling were determined by using a scanning electron microscope (SEM). Folding endurance8,9 The prepared patches were measured manually for folding endurance. The folding of the patches was repeated at the same place till they broke. The accurate value of folding endurance was given by the number of times the patches could be folded at the same place without breaking. Uniformity of thickness8The uniformity of thickness of transdermal patches was measured by micrometer with least count of 0-0.1 mm. At five different points the thickness of the patch was measured and the average of five readings with the standard deviation was calculated. Moisture content10 The prepared patches were marked, then individually weighed and kept in a vacuum desiccator containing diphosphorus pentoxide at room temperature for 24 h. The patches were individually weighed until they showed a constant weight. The percentage of moisture content was calculated as a difference between initial and final weight with respect to final weight. % of moisture content = (X-Y/Y) 100 Where, X = initial weight, Y = final weight. Moisture uptake10The weighed patches were kept for drying in vacuum desiccator at normal room temperature for 24 h upto a constant weight and then exposed to 84% relative humidity (saturated solution of potassium chloride). % of moisture uptake = (Y-X/X) 100 Where, X = initial weight, Y = final weight.

BAHAN DAN METODEMetformin hidroklorida diperoleh sebagai sampel hadiah dari Kemajuan Arcolab Ltd, Bangalore. Chitosan dibeli dari Sigma Aldrich, Bangalore. HPMC diperoleh dari Shreeji kimia, Mumbai, India. Dibutil ftalat diperoleh dari SD Fine Chemicals, Mumbai. Semua bahan kimia lainnya dan reagen yang digunakan dalam penelitian ini adalah kelas analitis.Persiapan Transdermal PatchJenis Matrix patch transdermal dari Metformin HCl disiapkan dengan teknik penguapan pelarut menggunakan proporsi yang berbeda dari polimer seperti Chitosan dan HPMC dalam cetakan kaca silinder dengan ujung terbuka di kedua sisi.Membran dukungan dilemparkan dengan menuangkan 5% (w / v) larutan PVA di bawah cetakan yang dibungkus dengan aluminium foil diikuti oleh pengeringan pada suhu 60 C selama 6 jam dalam oven. Rasio diperlukan dari dua polimer ditimbang dan mereka kemudian dilarutkan dalam etanol: diklorometana (1: 1) sebagai pelarut. Dibutil ftalat (20%) dari komposisi polimer digunakan sebagai plasticizer. Obat itu ditambahkan 20% b / b dari berat total polimer, dalam dispersi homogen, dengan pengadukan lambat pada pengaduk magnetik. Pada membran PVA dukungan dicor sebelumnya dispersi seragam (masing-masing 3 ml) dicor dan dikeringkan pada 40 C selama 6 jam. Setelah kering patch dikeluarkan dari cetakan, dibungkus dengan aluminium foil dan disimpan dalam desikator sampai mereka digunakan untuk studi lebih lanjut. Grafik formulasi diberikan dalam Tabel 1.Evaluasi Transdermal PatchObat polimer Interaksi Study7Kompatibilitas fisikokimia antara Metformin HCl dan polimer yang digunakan dalam film dipelajari dengan menggunakan transformasi-inframerah Fourier (FT-IR 8400, Shimadzu Co, Jepang) spektroskopi. Pellatization ini dilakukan dengan metode pelet KBr. Spektrum FT-IR tercatat di wilayah panjang gelombang antara 4000 dan 400 cm -1. Spektrum yang diperoleh untuk Metformin HCl dan campuran fisik Metformin HCl dengan polimer dibandingkan.Differential Scanning kalorimetriSekitar 5 mg sampel ditimbang dan berkerut ke panci aluminium dan dianalisis di kisaran pemindaian dari 0 C - 300C pada tingkat pemanasan suhu 5 derajat celcius / min di bawah aliran nitrogen dari 25ml / menit.Pemindaian mikroskop elektronRincian morfologi patch transdermal setelah pembengkakan ditentukan dengan menggunakan mikroskop elektron scanning (SEM).Endurance8,9 FoldingPatch siap diukur secara manual untuk daya tahan lipat. Lipat dari patch diulang di tempat yang sama sampai mereka pecah. Nilai akurat ketahanan lipat diberikan dengan jumlah kali patch bisa dilipat di tempat yang sama tanpa melanggar.Keseragaman thickness8Keseragaman ketebalan patch transdermal diukur dengan mikrometer dengan jumlah paling 0-0,1 mm. Pada lima poin yang berbeda ketebalan patch diukur dan rata-rata lima bacaan dengan standar deviasi dihitung.Kelembaban content10Patch siap ditandai, kemudian ditimbang dan disimpan dalam desikator vakum mengandung diphosphorus pentoksida pada suhu kamar selama 24 jam. Patch secara individual ditimbang sampai mereka menunjukkan berat konstan. Persentase kadar air dihitung sebagai perbedaan antara berat badan awal dan akhir sehubungan dengan berat akhir.% Dari kadar air = (X-Y / Y) 100Dimana, X = berat awal, Y = berat akhir.Kelembaban uptake10Patch yang ditimbang disimpan untuk mengeringkan dalam desikator vakum pada suhu kamar yang normal selama 24 jam upto berat konstan dan kemudian terkena 84% kelembaban relatif (larutan jenuh kalium klorida).% Dari serapan air = (Y-X / X) 100Dimana, X = berat awal, Y = berat akhir., X = initial weight, Y = final weight.