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Current Trends in Biotechnology and PharmacyVol. 5 (2) 1173-1182 April 2011. ISSN 0973-8916 (Print), 2230-7303 (Online)1177mm) free from air bubbles or physicalimperfections, was held between two clampspositioned at a distance of 3 cm. A card boardwas attached on the surface of the clamp toprevent the film from being cut by the grooves ofthe clamp. During measurement, the top clampat a rate of 2 mm s -1 pulled the strips to a distancetill the film broke. The force and elongation weremeasured when the films were broken. Resultsfrom film samples, which were broken at end werenot included in observations. The mechanicalproperties are calculated using equation 5 and 6.T.S.(Kg mm -2 ) = [Force at break (Kg) / Initial crosssectional area of the patch (mm -2 )].............(5)E.B (%mm -2 ) = [Increase in length (mm) / Originallength x 100 / Cross sectional area (mm 2 )]........(6)Preparation of rat abdominal skin: The animalstudy was conducted in accordance with theapproval of the animal ethical committee,Kakatiya University, India. Wistar rats weighing150–200 g were sacrificed using anaestheticether. The hair of test animals was carefullytrimmed with electrical clippers and the fullthickness skin was removed from the abdominalregion. The epidermis was prepared surgicallyby heat separation technique (12), which involvedsoaking the entire abdominal skin in water at 60 oC for 45 s, followed by careful removal of theepidermis. The epidermis was washed with waterand used for ex vivo permeability studies.Ex vivo permeation studies: Franz diffusion cellwith a surface area of 3.56 cm 2 was used for exvivo permeation studies. The rat skin wasmounted between donor and receptorcompartments of the diffusion cell with stratumcorneum facing the donor compartment. Thetransdermal patch was placed over the skin anda dialysis membrane (Hi-Media, Mumbai, India)was placed over the patch so as to secure thepatch tightly from getting dislodged from the skin(the transdermal patch was sandwiched betweenthe skin and dialysis membrane). The receivercompartment of the diffusion cell was filled with12 mL of phosphate buffer pH 7.4 containing 40% v/v polyethylene glycol (PEG) 400 and the setupwas placed over a magnetic stirrer withtemperature maintained at 37° C. PEG 400 wasincorporated to maintain sink conditions and thecontents of receptor compartment were agitatedat 400 rpm and was placed over a multi-magneticstirrer (Cintex, Mumbai, India). The study wasconducted at 37 o C and samples of 1 mL werecollected at preset time points and replenishedwith PBS (pH 7.4) containing 40 % v/v PEG 400.The cumulative amount of LCDP permeated wasdetermined using HPLC (7) and concentrationwas corrected for sampling effects according tothe equation 7 (13).C 1 n =C n [V T /V T -V s ][C1 n-1 /C n-1 ]....(7)where C 1 is the corrected concentrationnof the n th sample, C nis the measuredconcentration of LCDP in the n th sample, C 1 is n-1the corrected concentration in the (n-1) th sample.C n-1is the measured concentration of LCDP inthe (n-1) th sample, V Tis the total volume of thereceiver fluid and V Sis the volume of the sampledrawn.The steady state flux was calculated fromthe slope of steady state portion of the line in theplot of drug amount permeated Vs time.Permeability coefficient (Kp) was calculated bydividing the flux with dose. The lag time wascalculated from the intercept on the time axis inthe plot of cumulative amount permeated Vs time.The target flux was calculated using equation 8.Target flux = (Css x CLt x BW)/A.........(8)Css, the LCDP concentration at therapeuticlevel (8.6 µg L -1 ) and CLt the total body clearance,83.9 mL h -1 (calculated from volume ofdistribution, 2300 mL kg -1 and half life 19 h) (14),BW the standard human body weight of 60 kg, Arepresents the surface area of the diffusion cellDevelopment of matrix type transdermal patches of lacidipine
Current Trends in Biotechnology and PharmacyVol. 5 (2) 1173-1182 April 2011. ISSN 0973-8916 (Print), 2230-7303 (Online)1178(i.e. 3.56 cm 2 ). The calculated target flux valuefor LCDP was 12.16 µg cm -2 h -1 .FTIR studies: LCDP, ethyl cellulose, EudragitRL100, PVP, polymer mixture and physicalmixture of polymers and LCDP were placed inclear glass containers and exposed to 40 o C/75 %RH for 4 weeks. After 4 weeks, the samples weresubjected to FTIR studies by making pellets withKBr.Stability studies: The stability study for optimizedformulations (LE4 and LP3) was conductedaccording to the International Conference onHarmonisation (ICH) guidelines (15). Sufficientsamples of the formulations were wrapped inaluminium foil and stored in a petri dish at atemperature of 40 ± 2 o C/75 ± 5 % R.H (SkylabInstruments & Engineering Pvt Ltd, Thane, India)for 6 months. Samples were withdrawn at intervalsof 1, 2, 3, and 6 months and analyzed for drugcontent using the HPLC (7).Statistical analysis: Statistical comparisons weremade using Student’s t-test using Sigmastatsoftware (Jandel Corp., CA, USA). Results wereconsidered significant at 95 % confidence interval(p < 0.05) and results were expressed as mean ±SD.Results and DiscussionFormulation of transdermal patches of LCDP:Polymer films were formulated with varyingconcentrations of ethyl cellulose or ERL 100 andPVP. The experiment was initiated by taking 2gm of polymer and 90 mg of drug. As the polymerconcentration increased the films couldaccommodate more amount of LCDP.Precipitation of the drug was noticed with 2 g ofpolymer and when the polymer was increased,the precipitation was decreased. No precipitationwas observed with 2.5 g and above of the polymer.Therefore the amount of polymer selected was2.5 gm and in order to improve drug release PVPat different ratios was incorporated. The physicalappearance of the films was transparentsuggesting that the drug was completely solubilizedin the polymeric matrix. Based on preliminaryexperiments, d-limonene at a concentration of 8% v/w (showed maximum permeation of LCDPacross rat skin) was incorporated as penetrationenhancer.The results of weight variation test forvarious transdermal films are shown in Table 2.Results of weight variation test indicateduniformity in weight of the patches, as evidencedby RSD values, which were less than 6.Thickness of films varied from 201.3(LE1) to 210.4 µm (LE4); 185.6 (LP1) to 193.2µm (LP4) in respective series. The results (Table2) suggest that the change in polymer compositiondid not produce any significant effect (p>0.05)on the thickness. The thickness was found to beuniform as it was evidenced from RSD values,which were less than 6.The results of content uniformity areshown in table 1 and indicate good uniformity indrug content. The drug content was from 97.1 to101.5 % in formulation LE2 and LP3 respectively.In vitro drug release studies: The releaseprofiles of LCDP from transdermal patches wereCumulative amount of LCDP (µg) releasedTime (h)Fig 1. In vitro release profiles of LCDP transdermal patchesRamesh Gannu et al
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Page 133: (December 7-9, 2011)Venue: Karunya
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