Naphazoline Nitrate Nasal Gel Technology Using Kolkheti Sphagnum Peat Mineral Water

Transcription

1 Naphazoline Nitrate Naal Gel Technology Uing Kolkheti Sphagnum Peat Mineral Water R. Zazadze 1 ; N. Bakhtadze 2 ; A. Tertvadze 3 ; N. Alavidze 4 ; L. Ebralidze 5 ; A. Bakuridze 6 1,2,3,4,5,6 Department of pharmaceutical technology, Tbilii State Medical Univerity, Georgia Abtract-Depite the fact that flu i eaonal it i very maive. Almot everyone who i infected with flu ha rhiniti for which it i ued naphazoline nitrate. It i produced in a variety of doage form. Alo it i worth to notice that drop are quickly wahed from the naal cavity, and ointment ha more long proce and contact with the naal mucoa. To increae the effectivene the recent preference attach gel. Biopharmaceutical and technological reearche how Naphaoline nitrate 0.1% gel recipe and technology. Under normal torage we have tudied the tability of gel which were made on ditilled and peat water with Naphaoline nitrate 0.1%. It i etimated that the gel which i prepared on the peat water i table for a long time, than the gel prepared on the ditilled water. I. INTRODUCTION In modern pharmacy intranaal drug adminitration i becoming increaingly important. With noe mucu drug can be delivered in ytemic condition when it require le time in the appropriate doe (reach the concentration of active ubtance in the target organ or tiue). In addition, intranaal drug receiving i the mot appropriate, afe and convenient way, particularly for thoe drug which are not adminitered well (e.g. peptide, protein) in the other route except injection. Thi way i the bet alternative which help people to avoid injection and alo allow them to take medicine on themelve in a variety of dieae. Naal mucu good blood upply allow drug rapid aborption /2, 3/ Although the intranaal drug delivery ytem i characterized by a number of advantage there are alo ome factor uch a mucoal clearance, epithelial and mucoal barrier and enzymatic activity which affect negatively on drug delivery ytem and their ditribution. To overcome thi problem it i actually thoe drug elaboration uch a mucoadheive gel. Mukoadheive gel are binded to mucou membrane and finally the active of drug in the noe i increaing and improving /6/. Depite the fact that flu i eaonal it i very maive. Almot everyone who i infected with flu ha rhiniti for which it i ued naphazoline nitrate. It i produced in a variety of doage form. Alo it i worth to notice that drop are quickly wahed from the naal cavity, and ointment ha more long proce and contact with the naal mucoa. To increae the effectivene the recent preference attach gel. In hydrophilic gel compoition one of the component in mot cae i water. Alo peat mineral water i intereting for the reearche becaue of Kolkheti lowland phagnum peat (Ipani 2) water contain eential element: magneium, aluminum, ilicon, phophoru, ulfur, potaium, calcium, manganee, iron, copper, zinc and ilver and it ha antibacterial action /1,4,5,7/. II. RESEARCH PURPOSES AND OBJECTIVES The reearch purpoe repreent the elaboration of naphazoline nitrate naal gel recipe and technology uing Kolkheti peat ipani-2 mineral water. For purpoe accomplihment we mut olve the following tak: - Naal gel bae election baed on biopharmaceutical reearche uing Ipani-2 water; - Baed on the biopharmaceutical reearch naal gel recipe development uing ipani-2 mineral water; DOI : /IJRTER ZRP 84

2 International Journal of Recent Trend in Engineering & Reearch (IJRTER) Volume 03, Iue 03; March [ISSN: ] - Naal gel technology development uing Ipani 2 water - Naal gel tandardization and uitability timeframe in the ordinary condition of torage. III. THE RESEARCH OBJECTS AND METHODS The reearch ubject repreent Kolkheti lowland Ipani 2 mineral water, naphaoline nitrate ubtance and gel, auxiliary ubtance and material. For reearch method there are ued analyi phyical-chemical, intrumental and biopharmaceutical method: Determination of ph aqueou gel determination: we add 5 mg of gel to 50-50ml clear water in o C temperature, after carefully haking we have filtered twice in non-ah filter. We have tudied omotic feature in implified model (according to Kruvchinky). For control we have ued 10% olution of odium chloride. We were daily uing due to contant ma. We have full omotic activity gravimetrically and repreented in percentage which i relevant to ointment initial weight. We have determined a follow: we place in dializator (emiconductor membrane cellophane with diameter of 65mm, with pore ize of 0,025mm) 1,0g ointment, in dializator camera the ditilled water. Dializator wa in thermotatic condition during the whole period (37 0 C) and we were weighting with 1-hour interval. We were counting water which wa aborbed by the ointment in the difference in reult. Aborbed water we were counting by the formula: P = Where: P omotic preure; Mn at the moment of dializator camera ma i with reearch of ample (g) M0 dializator camera ma i before reearch of ample (g) Mn R at the moment of dializator camera ma i with control ample (g) M0 R - dializator camera ma i before reearch of ample (g) M Reearch ample ma. (g) For colloidal tability determination we have ued laboratory centrifuge. The tube wa filled 2/3, we were weighting with 0,01g accuracy (about 10g), placed it to water bath (42,5±2,5 С) for 20 minute, dry them and placed to centrifuge. Centrifugation wa performed for 5 minute in condition of 6000 r/min. Sample were conidered table if viually diection wa not oberved. We determined reearch ample thermotability a following: we took 5-6 gla tube with diameter 15mm and a height of 150mm, filled with reearch object with 8-10ml and placed in incubator (40 42) С for one week, then in refrigerator (10 12) С for one week too da kept there for 3 day at room temperature. Stability wa meaure viually if diection wa not oberved. Active ubtance releae from reearch object we have tudie by Franci diffuion cell. Reearch wa conducted a follow: the agg film wa ued a a membrane which we placed to 0,1 N hydrochloric acid for 36 hour (for calcium alt clearing to top the eparation of air bubble). With thi rule we have wahed egg with ditilled water. We have placed reearch object on the egg with 0,2-0,2g weight, ditributed evenly, placed between acceptor and donor and clamp it with pecial pin. We have applied acceptor label with ph phophate buffer in the meaning of 6,8. We have performed diffue thermotat within 37±0,1 0 C temperature. We have mixed diffue area with magnetic tirrer. We were taking ample every hour and added phophate buffer which wa equal to the ample. Analyzing ample optical denity wa determined by Shimadzu UV-1601PC on 280 nm wave length. Gel therapeutic propertie are depended on baement rational election becaue it ha a major effect on the peed and completene of the medicinal ubtance releae. Naphazoline gel i for naal mucoa ditance. That i why it i difficult for bae containing gel to contact with mucou membrane and becaue of that we have elected the hydrophilic nature bae (Table All Right Reerved 85

3 International Journal of Recent Trend in Engineering & Reearch (IJRTER) Volume 03, Iue 03; March [ISSN: ] Table 1.Napazolini nitrate gel compoition: Gel compoition component Compoition compound, gr Naphazoline nitrate 1,0 1,0 1,0 1,0 1,0 Hydroxypropylmethylcelluloe 1,5 Carboxymethyl celluloe 2,5 Sodium carboxymethyl celluloe 2,0 Carbopol 1,1 Sodium alginate 2,5 Sodium hydroxide 17% Water (ml) (Sphagnum- Ipani 2) 1,0 ml Gel preparation procedure with attending compoition: We add to polymer certain quantity alo a certain quantity of water and keep for aturation at room temperature. In the cae of carbomer we make it Alkali by odium hydroxide 17% olution in value of 6-7. Separately we prepare naphazoline pirit olutin for which we take a certain quantity and diolve it in 96 % pirit in a ratio of 1:10. During the tirring of gel we were adding naphazoline nitrate pirit olution and mixing it due to obtaining ma. Naphazoline nitrate intranaal gel determining phyical-chemical and technological characteritic are given in Table 2. Table 2 Naphazoline nitrate intranaal gel determining phyical-chemical and technological characteritic: Reearch preparation Baed on the peat water naal nitrate gel 0,1% Analyi pecification Analyi reult option Decription Identitie White homogeneou gel Analyzing and tandard ample olution aborption maximum hould be 270nm, 280nm, 287 nm and 291 nm on the wavelength matter Correpond Correpond Correpond correpond Correpond Correpond Correpond Correpond ph 5,8-7,0 6,4 6,0 6,1 6,7 6,5 Uniformity With naked eye viible incluion abence Correpond Correpond Correpond Correpond correpond correpond correpond Colloidal The abence Stable Stable Stable Stable All Right Reerved 86

4 Water aborbtion (%) International Journal of Recent Trend in Engineering & Reearch (IJRTER) Volume 03, Iue 03; March [ISSN: ] tability (viually) Thermotabilit y (viually) General requirement for the gel Quantitative determination of delamination The abence of delamination.f t.2 P Naphazoline nitrate content hould be 0,09-0,11% Stable Stable Stable Stable table Correpond Correpond Correpond Correpond Correpond 0,1% 0,105% 0.103% 0.101% 0.101% Table 1 data how that all reearch compoition atifie gel quality indicator. One of gel important feature i omotic effect preerence of abence. In the cae of firt phae of wound treatment omotic effect play an important role. Omotic activitie reult are hown at the Picture Time (hour) NaCl(10%) HPMC Na CMC Picture 1. Naphazoline nitrate reearch compoition omotic activity determination reult. Picture #1 how that natrium chloride 10% olution conumed only 12,7% of water for the firt two hour. After a periodi growth i no longer oberved. Baed on hydroxypropylmethil-celluloze gel i characterized by high omotic activity, for 12 hour water wa conumed in 108%. A for the gel, which are made of carboxymethylcelluloe, Sodium alginati, karbopholy and natrycarboxylmethilcelluloze they have the ame omotic activity in the identicit period (12 hour) conumed equal to % of water. For optimal compoition election we have tudie the dynamic of the releae of Naphaoline nitrate from gel uing diffuion cell. Reult are reflected on Picture 2. CMC Na Alginate All Right Reerved 87

5 Rreleae (%) International Journal of Recent Trend in Engineering & Reearch (IJRTER) Volume 03, Iue 03; March [ISSN: ] t (minute) Carbopol CMC Na CMC Na alginate HPMC Picture 2. The dynamic of the releae of Naphaoline nitrate from gel. Reult (Picture #2) how that Naphaoline nitrate releae from carbomer containing gel i virtually on zero tatu. Celluloe item bae are in advantage. The bet reult of active ubtance releae will be when natrium carboxymethylcelluloe will be ued. Therefore, further tudie will continue in #3 compoition. For naphaoline nithrate gel technological and conumer characteritic predicting we tudied rheological characteritic. For tudy we have ued SNB 2 (Picture 3). We have determined at room temperature (20 0 C) and 34 0 C (the temperature of human kin) Diplacement tenion, Pa Diplacement peed ec 1 Picture 3. Naphaoline nitrate gel rheogram. The gel Rheogram (Picture #3) how that the vicoity i harply dropped with the increae of deformation, at the ame time the tenion of diplacement i increaing. Such an attitude demontrate the tructured ytem. Baed on the experimental reearche Naphaoline nitrate gel technology i hown in the following: Naphaoline nitrate and Sodium carboxylmethylcelluloe are immunized on the vibration ieve. Ethyl pirit and the peat water i meaured by the flak. Sodium carboxylmethylcelluloe i prepared in 2,0% olution: ditilled water i placed in Sodium carboxylmethylcelluloe and i detained for one day and night. Separately Naphaoline nitrate pirit olution i made: Naphaoline nitrate 0,1g i diolved in 96% ethyl pirit. The next day we add to carboxylmethylcelluloe aturated olution Naphaoline nitrate pirit olution with contant tirring. Homogenization it due to gel and determine preparation quality indicator. Naphaoline nitrate 0.1% in intranaal gel Naphaoline nitrate content hould be All Right Reerved 88

6 International Journal of Recent Trend in Engineering & Reearch (IJRTER) Volume 03, Iue 03; March [ISSN: ] On the next tage of the reearch we have tudied Naphaoline nitrate gel tability in normal torage. We have tudied tability of Naphaoline nitrate gel made in purified and peated mineral water. The reearch wa conducted during one year. We etablihed that with peat Naphaoline nitrate 0.1% made on peat mineral water gel tability wa 250C (60%/RH) during 12 month, but 0.1% Naphaoline nitrate naal gel prepared on the ame condition i untable in the eventh month. IV. CONCLUSIONS Biopharmaceutical and technological reearche how Naphaoline nitrate 0.1% gel recipe and technology. With quality characteritic: uniformity, identity, water ph, colloidal and thermaltability, omotic activity, vicoity, the active ubtance releae kinetic, quantitative content, Naphaoline nitrate 0.1% gel which atifie NTD- requirement. Under normal torage we have tudied the tability of gel which were made on ditilled and peat water with Naphaoline nitrate 0.1%. It i etimated that the gel which i prepared on the ditilled water i table for 6 month, but on the peat water for 12 month. REFERENCES 1. Влияние сфагновых торфяных ресурсов на бактерии вызывающие нозокомиальные инфекции в сравнении с современными антибиотиками/ Ломтадзе Л.Б., Церцвадзе А.М., Ахвледиани Л. Т., Коиава Т.Н., Джохадзе М.С., Бакуридзе Л. А., Берашвили Д.Т., Бакуридзе А. Д.//,, Medication to Human. Modern Problem Pharmacotherapy and Precribed of Medication.Kharkiv, Ukraine Illum L. Naal drug delivery: new development and trategie. Drug Dicov Today. 2002; 7: Illum L. Naal drug delivery: poibilitie, problem and olution. J Control Releae. 2003;87: Kaffke, A. (2008): Vegetation and ite condition of asphagnum percolation bog in the Kolkheti Lowland(Georgia, Trancaucaia). Phytocoenologia. 38: De Klerk Pim, Andrea Haberl, Andrea Kaffke, Matthia Kreb, Izolda Matchutadze, Merten Minke, Jenny Schulz, Han Jooten. Vegetation hitory and environmental development ince ca 6000 cal yr BP in and around Ipani 2 (Kolkheti lowland, Georgia). Quaternary Science Review 28 (2009) Marttin E., Nicolaa G.M., Schipper J., Coo V., Fran WH. Naal mucociliary clearance a a factor in naal drug delivery. Adv Drug Del Rev. 1997; 29: Mineral Reource (Peloid and Clay) of Adjara Region/ T Maiukovichi, A. Gaprindah-vili, A. Tertvadze, G. Kamkamidze, N. Inanahvili, N. Poporadze, D. Berahvili// 3 rd Interna-tional Conference on Pharmaceutical Science (ICPS 2015). Tbilii State Medical Univerity, All Right Reerved 89