Formulation And Evaluation Of Fast Dissolving Films Of Loratidine By .

ISSN: 2277- 7695CODEN Code: PIHNBQReceived: 10-01-2013Accepted: 23-03-2013ZDB-Number: 2663038-2IC Journal No: 7725Vol. 2 No. 2 2013Online Available at www.thepharmajournal.comTHE PHARMA INNOVATION - JOURNALFormulation and Evaluation of Fast Dissolving Filmsof Loratidine by Solvent Casting MethodP. Narayana. Raju*1 , M. Sravan Kumar1, Ch. Madhusudhan Reddy1,and K. Ravishankar11.Department of Pharmaceutics and Industrial Pharmacy, KLR Pharmacy college, Paloncha, KhammamDist. Andhrpradesh, India[E-mail nrpadala@rediffmail.com]Fast dissolving films have been played an important role in the current pharmaceutical research. They haveconvenience and ease of use over other dosage forms such as orally disintegrating tablets and immediate releasetablets. In the present research, rapidly dissolving films of loratidine were developed using low viscosity grades ofHPMC as film forming polymers. HPMC is a water soluble synthetic polymer which was used as film former formmany years. The films of loratidine were prepared by solvent casting method using di-chloromethane and methanolas solvents. The prepared films were evaluated for drug content, weight variation, thickness and in vitro in vivodisintegration time. Loratidine is moderately bitter drug, taste masking was achieved by use of sweeteners, flavoursand citric acid. Type of flavor significantly affected the taste masking propderty. The in vitro and in vivodisintegration time of the optimized formulation was found to be below 29 seconds and 24 seconds respectively. Theprepared films exhibited good integrity and thickness. In vitro dissolution studies were performed as per the FDAdissolution guidelines for about 10 minutes, the optimum formulation released complete drug with in 4-6 minutes.DSC and FTIR studies showed no drug polymer interaction.Keyword: Fast Dissolving Films, Loratidine, HPMC, Solvent Casting, Taste Masking1. IntroductionFast dissolving films or rapidly dissolving dosageforms have greatimportance in thepharmaceutical industry due[1,2] to their uniqueproperties and advantages. They undergo rapiddisintegration in the salivary fluids of the oralcavity in less than a minute, where they releasethe drug. Most of the drug is swallowed orallywith the saliva and the absorption of drug takesplace in the gastro-intestinal [3.4] tract. The fastdissolving dosage forms are referred by variousnames by researchers like quick disintegrating,orally disintegrating, rapidly disintegrating,mouth dissolve or melt in mouth dosageforms[1,3,4].Vol. 2 No. 2 2013These rapidly disintegrating formulations havingcertain specific advantages like no water requiredfor taking the dosage form, accuracy, immediateavailability of drug at the site of absorption, rapidonset of action, ease of handling and transporting,acceptable pleasant taste and improved patientcompliance. The dosage forms were firstintroduced in 1970's as an alternative to theconventional immediate release tablet andcapsule which[3-5], require swallowing of thedosage form. The lyophilized dosage forms suchas wafers, thin strips and films are newlydeveloped technologies for the rapidly dissolvingdosage forms. These dosage forms can bemanufactured using a variety of technologies,www.thepharmajournal.comPage 31

The Pharma Innovation - Journalincluding freeze drying, vacuum drying, spraydrying[1,2] by using different super disintegrentsand molding methods.Fast disintegration dosage forms are available inthe market for a variety of drugs. Orallydisintegrating films were introduced in the marketas breath fresheners and personal care productssuch as dental care strips and soap strips.However these dosage forms are introduced inthe United States and European pharmaceuticalmarkets for [2,5-7] better therapeutic benefits. Theoral disintegrating films are prepared using watersoluble and/or water swellable film formingpolymer due to which the film dissolves rapidlywhen placed on the tongue in the oral cavity. Thefirst oral strips were developed by the Pfizer whonamed it as Listerine and were used for mouthfreshening. Chloraseptic relief strips were thefirst oral thin films which contained[7] benzocaineand were used for the treatment of sore throat.Hydroxy propyl methyl cellulose is the watersoluble swellable polymer which was used as afilm forming agents at low viscosity. The mostpreferred grades of HPMC film formers areHPMC E 3, HPMC E6 and HPMC E 15[8,9].These polymers were easily soluble in the waterand gives viscous clear solution.Loratadine is used in the treatment ofallergy[10,11]. Fast dissolving films of this druggives better therapeutic benefits for the pediatricand bedridden or developmentally disabledpatients. Thus, a FDF would serve as an idealdosage form for the patients as well as paediatricpatients who find it difficult to swallow the tablet.Due to its ease of usage and high acceptability,FDF of Loratadine was formulated in the presentinvestigation.2. Materials and methods2.1 MaterialsLoratadine was received as a gift sample fromStrides acrolabs Banglore, India. HPMC gradeswere received as a gift sample from Colorcon asiaPVT Ltd, Goa, India., polyethylene glycol 400(PEG 400) were purchased from S.D. Fine ChemLtd., Mumbai, India. Aspartame was purchasedfrom Himedia Lab Pvt Ltd., Mumbai, India.Orange flavour was received as gift samples fromVol. 2 No. 2 2013Pentagon trading company, Ahmedabad, India.All other chemicals used were of analytical gradeand were used without further purification.2.2 Methods2.2.1 Preparation of ODFThe FDF of Loratadine were prepared usingHPMC E3, HPMC E6 and HPMC E15 withdifferent ratios of 1:3, 1:6 and 1:9. The polymericsolution of HPMC was prepared by usingdichloromethane and methanol in the ratio of 1:1and kept aside for about 5 to 6 hrs for swelling ofpolymer. Loratadine was dissolved in 4 ml ofdichloromethane and this drug solution wasadded to the above polymeric solution. This stepwas followed by the addition of plasticizers suchas PEG 400, sweetener, flavor and colour wasadded. Uniformity of drug content is achieved bymixing in cyclo mixer for 10 minutes. Thesolution was cast on a petri dish and dried at450C in hot air oven for 45 minutes. The filmwas carefully removed from the petri dish, thenchecked for imperfections and cut to the requiredsize to deliver the equivalent dose (2.5 2.5 cm2)per strip. Film samples with air bubbles, cuts orimperfections were excluded from the study.2.2.2 Evaluation of ODFThickness EvaluationThe thickness of the FDF was evaluated usingdigital vernier calipers (Mitutoyo, Japan) TheFDF sample equivalent to dose of the drug wastaken and the average of three readings was takenas mean thickness. The results are shown in TableNo.1 and 2.2.3 In Vitro Disintegration Studies[2]Disintegration time gives an indication about thedisintegration characteristics and dissolutioncharacteristics of the film. The film as per thedimensions required for dose delivery was placedon a stainless steel wire mesh placed in apetridish containing 10 ml distilled water. Timerequired for the film to break was noted as invitro disintegration time in Table No.1.www.thepharmajournal.comPage 32

The Pharma Innovation - JournalTable 1: Formulation characteristics of the prepared fastdisintegrating films of LoratadineIngredientsF1HPMC E3DCM*Methanol*PEG 400AspartameOrange flavorLoratadineHPMC E6DCM*Methanol*PEG 400AspartameOrange flavorLoratadineHPMC E15DCM*Methanol*PEG 400AspartameOrange flavor100300128F2Quantity in 10504010F6100900128504010F9100900128504010* Processing solvent in the preparation of films, notpresent in the final formulation.Table 2 Physico chemical characteristics of the preparedfast disintegrating films of LoratadineCode Thickness AssayDT(mm)(%) In vitro In F80.17996459F92.4 In Vitro Dissolution StudyIn-vitro dissolution study of the prepared FDFformulations was carried out by the methodVol. 2 No. 2 2013suggested by USFDA [12] dissolution methods forLoratadine. The method was USP type I (basket)by using Electro lab dissolution rate testapparatus. FDFs of desired formulation weretaken and placed in the wire mesh of 700 μm andthen it was placed in the vessels of dissolutionapparatus. Samples were collected from thevessels at 2, 4, 6, and 10 minutes , replaced withsame volume of the blank solution. The solutionswere filtered through millipore 0.45 µm syrangefilter and analyzed using UV – Visspectrophotometer. Drug concentration wascalculated from the standard graph and expressedas % of drug dissolved. The release studies wereperformed in 6 replicates and mean values weretaken.2.5 Fourier Transform Infrared Spectroscopy(FT-IR)The FT-IR spectrum of pure drug and preparedFDF formulation were determined.FTIR(Thermo nicolet 670 spectrometer) was used forthe analysis in the frequency range between 4000and 400cm-1 and 4cm-1 resolution. A qualityequivalent to 2 mg of pure drug was used for C)Thermal properties of pure drug and theformulation were evaluated by Differrententialscanning colorymetry (DSC) using a diamod(DSC) (Mettler star sw8.10).The analysis wereperformed at a rate 50C min-1 to 200oCtemperature range under nitrogen flow of 25mlmin-1.3. Results and DiscussionThe Loratadine FDFs were prepared andevaluated for various physico chemicalproperties. The prepared formulations showeduniform distribution of the drug throughout thefilm. In vitro dissolution of the prepared FDFs F1 and F-2 prepared at 1:3 and 1:6 drug polymerconcentration released the complete drug in 6minutes. As the drug is rapidly absorbed form theGI tract, the initial dissolution time points werevery important. The formulation F-3 preparedwww.thepharmajournal.comPage 33

The Pharma Innovation - Journalusing 1:9 ratio released only 89 % of the drug in10 minutes. In case of formulations prepared withHPMC E6, the formulations F-4 was released thecompleted drug in 10 minutes where as theformulation F-5 and F-6 released only 88 % and70 % respectively with in 10 minutes. Theformulation prepared with HPMC E 15 (F-7- F-9)was unable to release the complete drug with in10 minutes due to its increased polymer viscosity.This clearly indicated the drug release from FDFwas mainly depends on the polymer viscosity andthe concentration of the polymer used in theformulation. Plots for the cumulative drugreleased vs time were showed in Figure1.The prepared ODF showed better film formingproperty due to the addition of PEG 400. Theprepared films showed uniform distribution of thedrug with out uneven shape and air entrapmentsas shown in figure 2 The thickness of all theformulation was found between 0.11 to 0.17 mm.The thickness was increased as the polymerproportion increased. In vitro and in vivodisintegration of the formulation prepared withHPMC E 6 was below 39 sec and 35 secrespectively. The taste masking of theformulations was achieved by using aspartame. Invivo taste evaluation showed better taste than thepure drug.F1F4F-7F2F5F-8Fig 2: Photographs Showing the Prepared Fast DissolvingFilms of LoratadineThe prepared formulations were evaluated forDSC and FTIR studies. Results of the DSC studyof pure drug showed sharp endothermic peak at134.8OC. Similar endothermic peaks wereobtained in the formulations at 134.4OC clearlyindicated that there was no drug polymerinteraction. Results of DSC thermograms wereshowen in the Figure 3.F3F6F-9Cumulative percent released100806040200024610Time (Minutes)Fig 3: DSC thermograms of pure Loratadine andLoratadine Fast disintegrating filmsFig 1: In Vitro Dissolution Profiles of the Prepared FDF ofLoratidineVol. 2 No. 2 2013The FTIR spectrum of pure Loratadine showed1703cm 1 (C O of ester), 1560 and 1474cm 1(stretching vibrations of benzene ring), andwww.thepharmajournal.comPage 34