Nghiên cứu bào chế và đánh giá sinh khả dụng viên nang aciclovir tác dụng kéo dài

Luận văn

   **********   VIÊN NANG ACICLOVIR   1    **********   CLOVIR     PGS.  GS TS. Võ Xuân Minh 1 i LLI CM N Tôi xin bày t lòng bic: PGS. TS. Phm Th Minh Hu GS. TS. Võ Xuân Minh Nhi thng dn và h tôi trong thi gian làm lun án va qua. xin chân thành c Nguyn Trn Linh cùng toàn th các thy, cô giáo, k thut viên B môn Bào ch, b c lc , tu kin thun li cho tôi hoàn thành lun án này. Trân trng c , tu kin ca TS. Phùng Th Vinh, ThS. Nguyn Th Thanh Tho cùng các kim nghi     c, Vin Kim nghim thu Tôi xin chân thành c      ng, PGS. TS. Nguyn Thanh Bình, TS. Nguy ti h tôi trong quá trình công tác, hc tp và nghiên cu. Cui cùng, tôi xin cn bè       ng viên, to m u kin thun l  tôi hoàn thành lun án. Hà N  Thu Giang ii L   u ca riêng tôi. Các s liu, kt qu nêu trong lun án là trung thc ai công b trong bt k công trình nào khác.  Thu Giang iii DANH MC CÁC KÝ HIU, CH÷ VIÕT T¾T ACV : Aciclovir ACV-KDNM :  AUC :  BAK : Benzalkonium clorid BP : (British Pharmacopoeia) C-974 : Carbopol 974P NF C max :  CMC : Carboxymethyl cellulose  :  DM : Dung môi DBP : Dibutyl phtalat EBV : Virus Epstein-Barr EC : Ethyl cellulose EDTA : Acid ethylendiamintetraacetic FDA : – Food and Drug Administration) GPDC :  GPKD :  HPCD : 2-hydroxypropyl E-cyclodextrin HPLC : high performance liquid chromatography) HPMC : Hydroxypropyl methyl cellulose HQC : cao (high quality control sample) HSV : Virus Herpes simplex HT :  KDNM :  Kl/kl :  Kl/tt :  KSGP :  KT :  KTT :  LLOQ : lower limit of quantification) LQC : low quality control sample) iv MEC : minimum effective concentration) MQC : middle quality control sample) MRT :  (mean retention time) MTC : minimum toxic concentration) NaDC : Natri deoxycholat NaGC : Natri glycocholat NaLS : Natri laurylsulfat NTN :  OCC : DL-octanoylcarnitin clorid PCC : Palmitoyl-DL- carnitin clorid PEG : Polyoxyethylen glycol PEPT :   P-gp : P-glycoprotein PVA : Polyvinyl alcol PVP : Polyvinyl pyrolidon K30 RSD : relative standard deviation) SCC : DL-stearoylcarnitin clorid SD :  (standard deviation) SKD :  SMEDDS :  (self-microemulsifying drug delivery system) STT :  T 1/2 :  TBA : 4-thiobutylamidin TCCS :   :  TEC : Triethyl citrat TEER :  (transepithelial electrical resistance) T max :  TT :  Tt/tt :  USP :  (United States Pharmacopeia) VA : Viên nén Vacrax ® 200 mg VKNTTW :  VZV : Virus Varicella- zoster WHO :  (World Health Organization) v   .1 CHNG NG QUAN .3 1.1. ACICLOVIR 3 aciclovir 3 aciclovir  7  20  .20   .21  22 aciclovir  24 T 28  28 1.3.2 .28  31 aciclovir .35 CH     VÀ PHNG PHÁP NGHIÊN  .39  .39  39  .40   .41  41 2.2. PH .41 2.2.1. Ph .41 2.2.2. Ph 44 2.2.3. Ph .47 2.2.4. Phin vivo  .50 2.2.5. Ph 53 2.2.6. Ph .54 CH .55 CLOVIR .55 vi aciclovir 55  60  62 . 68 aciclovir  .68 aciclovir 200 mg GPKD 87   .89 g ph  .89   .94  .103  .104 3.4.1. Theo dõi hàm l 104 3. .107  .110 3.5.1. ng 110  .121 CH .130 NGHIÊN CLOVIR .130 CLOVIR GPKD 134   .138  .141  .141  146  . 147  .148  156 vii   aciclovir  o  4  aciclovir -2 4 1.3. aciclovir 7                aciclovir 37 5.  39 6.  45 7.   app ) 56 8.  57 .  58 .  59 11.   61 .  63 .               64 .   66 .  67 .   69 .  70 .   70 .  71 .   72 .  73 viii . màng bao GPKD  74 .  74 . GPKD  khác nhau 75  3.25.  77 6.  77 7. T 78 8.  bao GPKD 79 29.  GPKD 80  3.30.  81 1.  86 2.  86 3.   87 4.  GPKD 88 3.35. ACV   90 6.   91 7.   92   94 .   95 .  khí vào khác nhau 97 .  khí phun khác nhau 98 3.42.                99 .   100 .  và  viên nang aciclovir  các  tiêu sau: 1. B  viên nang aciclovir 200 mg GPKD.  200 mg/5ml 4 Zoraxin Viên nén 200, 400 và 800 mg Valor Pharmaceuticals Kem 5 %, tuýp 2g và 10g 5 Aciclovir Stada Viên nén 200 và 800 mg Stada –VN Kem