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Preparation and Evaluation of Liposome Containing Clove Oil

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Preparation and Evaluation of Liposome Containing Clove Oil PREPARATION AND EVALUATION OF LIPOSOME CONTAINING CLOVE OIL By Pilaslak Akrachalanont A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree MASTER OF PHARMACY Program of Pharmaceutical Technology Graduate School SILPAKORN UNIVERSITY 2008 PREPARATION AND EVALUATION OF LIPOSOME CONTAINING CLOVE OIL By Pilaslak Akrachalanont A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree MASTER OF PHARMACY Program of Pharmaceutical Technology Graduate School SILPAKORN UNIVERSITY 2008 !"#$% &'(% !)%*+!,-.&"-#,//1(",$3 .!('1( $3! ,!" 4"-#2552 .)6.&$3! ,!" The graduate school, Silpakorn University has approved and accredited the thesis title of Preparation and Evaluation of Liposome Containing Clove Oil submitted by Miss Pilaslak Akarachalanon as a partial fulfillment of the requirements for the degree of master of pharmacy, program of pharmaceutical technology. (Associate Professor Sirichai Chinatangkul, Ph.D.) Dean of graduate school ./.../... The Thesis advisors 1. Associate Professor Somlak Kongmuang, Ph.D. 2. Assistant Professor Police Captain Malai Sathirapund 3. Associate Professor Uthai Sotanaphun, Ph.D. The Thesis Examination Committee Chairman (Parichat Chomto, Ph.D.) ../../.. .Member (Prof. Garnpimol Rittidej, Ph.D.) ../../.. .Member (Assoc.Prof. Somlak Kongmuang, Ph.D.) ../../.. .Member Member (Assist.Prof. Pol.Capt. Malai Sathirapund) (Assoc.Prof. Uthai Sotanaphun, Ph.D.) ../../.. ../../ 47353202 : MAJOR : PHARMACEUTICAL TECHNOLOGY KEY WORDS : LOPOSOME / CLOVE OIL / EUGENOL / THIN FILM METHOD PILASLAK AKRACHALANONT : PREPARATION AND EVALUATION OF LIPOSOME CONTAINING CLOVE OIL. THESIS ADVISORS : ASSOC.PROF.SOMLAK KONGMUANG, Ph.D., ASSIST.PROF POL.CAPT. MALAI SATHIRAPUND, AND ASSOC.PROF. UTHAI SOTANAPHUN, Ph.D. 117 pp. This research particularly focuses on preparation of liposomes which can efficiently maintain stability and quality of clove oil. The research method used in this study can be divided into five main steps. First, phosphatidylcholine(PC) was purified by chromatpographic techniques. Each source of PC was chemically evaluated following to Bartlett’s assay and densitometry. Second, liposomes from three different sources of PC (i.e., purified PC from commercial PC(PPC), commercial PC(CPC) and commercial high-purified PC(HPC)) were prepared by using two different methods: thin film method and reverse evaporation. Four different molar ratios of PC to cholesterol: 1:0, 9:1, 7:3 and 1:1 were investigated. Third, size and size distribution control analyzed by extruding liposomes obtained from the two techniques through syringe extruders. Fourth, a physical study of liposome containing clove oil was performed using transmission electron microscopy (TEM), a chemical analysis of eugenol was performed using gas chromatography (GC) and a stability study was performed at a temperature of 4 °C for 3 months. Finally, release of clove oil from liposome was studied using in vitro release apparatus. The research results showed that PPC, CPC and HPC contained 68.67±3.90%, 39.00±4.38% and 70.00±4.25% of PC respectively. The densitometer data of three types of PC were shown to be in the same pattern as those of Bartlett’s assay. Thin film method and 1:1 molar ratio of PC to cholesterol showed multilamellar structure in the liposome from every source with size of 204.32±259.82, 246.99±125.16, 243.45±165.76 nm. for PPC, CPC and HPC respectively. The multilamellar structure of liposome analyzed by using TEM showed that liposome from PPC and CPC were similar to that from HPC while liposome prepared by CPC showed incomplete multilamellar structure and high polydispersion index (PI) with size of 200.76±0.58, 200.23±0.19 and 200.35±0.43 nm with extruded PPC, extruded CPC and extruded HPC respectively. The results showed that liposome extruded through a syringe extruder had low PI since size of liposome was controlled by membrane. In addition, results of the chemical study showed that the amount of eugenol contained in the liposome from PPC was nearly equivalent to that contained in the HPC. After storage, in 4 °C for 3 month the morphology of liposome from each type of PC did not change significantly. Liposome prepared by HPC or PPC could maintain eugenol with sustained release pattern within 4 hours were released 87.74%, 77.76% and 74.96% of eugenol, respectively. Thus, PPC could be a good source for liposome as comparing to HPC in term of quality of containing substance and stability. Program of Pharmaceutical Technology Graduate School, Silpakorn University Academic Year 2008 Student’s signature……………………………………………………… Thesis Advisors’ signature 1………………… 2………………….…3………..………… d 47353202 : : / / ! "#$% !% : &'**+-68. !%-9#;% : ". <. #$% =>!= '* +"..&.!.?= @;8% '* ". <. !8 ;*;8%. 117 ?B. "9#&-68 '6F="9#!!H 5 &! &!' <IJ!!!N!N<<QB&NNVW < PC -<B688$ <QB BartlettYs assay '* Densitometry &!-!=& PC 3 '?F= >! PC -< PC 68;Z&-(PPC) , PC 68;Z&-(CPC) '* PC 68;Z=(HPC) <QB;& 2 ; >! Thin film method '* Reverse phase evaporation =6!&F<*?F= PC '* !&!! 4 !&F >! 1:0, 9:1, 7:3 '* 1:1 &!-<<'*68< !=-&<B= 2 ; &!-- -68-&<B"9#= <QBB!=8"%!]&!'66F!=+F'**?%=<QB^&NNV Q?$!9-=HQ &!8<B"9#<F! !! <QB !8$%"9#<F!!F= +"9#6F PPC, CPC '* HPC $N!N!F6 B!* 68.67±3.90, 39.00±4.38 '* 70.00±4.25 &<6 ;&'66 Thin film method -!&F 1:1 Q?B <+=? <<!= >! 204±259.82, 246.99±125.16 '* 243.45±165.76 & &<6 *8$6&= 6F& PPC '* CPC #$* ?>!6 HPC '&F-& CPC #$*+=-F6$% '*F*&=F -& PPC '* HPC >-!68<!= <!8+F liposome extruder 6FQ?B*<'6= 9-=<<BFPI -<= <<!=!= extruded PPC, extruded CPC '* extruded HPC 200.76±0.58, 200.23±0.19 '* 200.35±0.43 & &<6 "9# =6F-& PPC @68 EU <BQB=6-& HPC ?= <=&- 4 !=" H 3 <>! 6FF=!=8'?F=!= PC F -'= <F! EU -& HPC, PPC '* CPC B!* 87.74, 77.76 '* 74.96 &<6 H<F!'66 Sustain release Q 4 -= "9#8<BF PPC @ &-@68'*=&6F-& HPC 6$z& ?" V"9# 2551 >!>-!"9#. >!>-!!%-9#;% 1.. 2.3.. e ACKNOWLEDGEMENTS Oooooooo This thesis was successfully achieved through the cooperation of many individuals. First of all, I would like to express my appreciation to my major advisor, Associate Professor Dr. Somlak Kongmuang for his encouragement, patience, valuable comments and support given throughout my time in graduate school. Oooooooo I also would like to thank my co-advior, Assistant Professor Police Captain Malai Sathirapund and Associate Professor Dr. Uthai Sotanaphun for his meaningful consultancy, helpful comments and suggestion.An appreciation is extended to Professor Dr. Garnpimol Rittidej for her moral support, the creative guidance, and encouragement. Oooooooo To all my teachers, fellow graduate students and the staff in Faculty of Pharmacy, Silpakorn University, I would like to thank them for their support, assistance and friendship over the years. Oooooooo Appreciation is also due to Mrs. Malee Bunjob, the director of Herbal Medicinal Research Institution for her permission and support for my graduate education. Special thanks would go to all persons in the Herbal Medicinal Research Institution, who have not been mentioned here for kindness and support. Oooooooo Finally, I would like to express my deep gratitude and appreciation to my parents , my brother and my sister for their attention and loving support. f CONTENTS Page English Abstract .... d Thai Abstract e Acknowledgement.. f Contents.. ... g List of Tables. h List of Figures. .. j Chapter I Introduction..... 1 II Review of literature........................................ 3 III Materials and method.. 28 IV Results..... 36 V Discussion... 63 VI Conclusion. 71 Bibliography.. 73 Appendices. 81 Biography.. 117 g LIST OF TABLES Table Page 1 Inorganic phosphorus content of PPC, CPC and HPC.... 38 2 Phosphatidylcholine content of PPC, CPC and HPC.. 40 3 Data Comparison between Phosphatidylcholine content determined ooooooooby Bartlett's assay and TLCdensitometry... 40 4 Morphology of liposome prepared by thin film method and reverse phase ooooooooevaporation method at various ratio of phosphatidylcholine oooooooocholesterol .. 47 5 Particle size of liposome from PPC (nm)... 48 6 Particle size of liposome from CPC (nm)... 48 7 Particle size of liposome from HPC (nm)... 49 8 Particle size of 1:1 (PC:cholesterol) extruded liposome prepared from various ooooooootype of lecithin using thin film method.. 49 9 Centrifugal condition of separation of excess clove oil from liposome.... 50 10 The result of the addition of different clove oil into1:0 (HPC:cholesterol) ooooooooLiposome.... 50 11 The result of the addition of different clove oil into7:3 (HPC:cholesterol) ooooooooLiposome.... 51 12 The result of the addition of different clove oil into1:1 (HPC:cholesterol) ooooooooLiposome.... 51 13 The result of the addition of different clove oil into1:0 (PPC:cholesterol) ooooooooLiposome..... 52 14 The result of the addition of different clove oil into7:3(PPC:cholesterol) ooooooooLiposome. 52 15 The result of the addition of different clove oil into1:1 (PPC:cholesterol) ooooooooLiposome. 53 16 The result of the addition of different clove oil into1:0 (CPC:cholesterol) ooooooooLiposome. 53 h Table Page 17 The result of the addition of different clove oil into7:3 (CPC:cholesterol) ooooooooLiposome. 54 18 The result of the addition of different clove oil into1:1 (CPC:cholesterol) ooooooooLiposome. 54 19 Comparison the maximum amount of clove oil between HPC liposome ooooooooand PPC liposome... 55 20 Quality control of clove oil (determined % eugenol in clove oil, triplicate ooooooooStudy PPC liposome... 57 21 Eugenol in clove oil containing in liposome from PPC, CPC and HPC 57 22 Stability study of eugenol content in liposome... 59 23 Study of gradient mobile phase for extraction commercial lecithin... 86 24 %Yield of lecithin from gradient mobile phase.. 87 25 Study of extraction lecithin from 9:1(chloroform:methanol) as mobile phase 87 26 %Yield of lecithin from 9:1 as mobile phase... 87 27 Study of extraction lecithin from 4:1(chloroform:methanol) as mobile phase 88 28 %Yield of lecithin from 4:1 as mobile phase.. 88 29 Absorbance data of standard curve. 95 30 Absorbance data of phosphatidylcholine and weight of inorganic phosphorus.
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