2769 TTS (Transdermal( Therapeutic System) 의개발및응용 제일약품 ( 주 ) 중앙개발연구소수석연구위원장병모
2770 - 목차 - A. TTS 개요 A-1. TTS 정의및장 / 단점 A-2. TTS 의종류및응용 B. TTS 제형개발및제조공정 B-1. 개발공정 B-2. 제조공정 (Coating Type)
2771 A. TTS 개요 A-1. TTS 의정의및장점 * 정의 경피흡수체계 (Transdermal Therapeutic System : TTS) * 장점 약물을일정한형태로피부에적용하여피부흡수를통하여전신작용효과를얻고자한 약물전달체계 (Transdeermal Drug Delivery System ; TDDS, TDS) 를말한다. 1 위장관의 ph, 효소, 장내세균등의방해없이약물을체내에전달가능함 2 주사제의위험성, 불편성배제및경구투여시흡수, 대사차이에의한개체편차가적다 약물투여간편및전신부작용감소 3 약물투여가연속적이므로반감기가짧은약물의적용가능함 4 약물의투여량과흡수속도가조절가능하며 3일이상지속성유지가능함 유효혈중농도유지및위장 / 간장애감소 5 필요시약물투여차단용이 * 단점 ( 개발과제 ) 1 피부한계성 본질적인피부 barrier 기능 2 약물의한계성 낮은경피흡수율 3 피부자극성완화 피부부작용 ( 발적, 발진 ) 4 피부부착성개량 발한, 목욕등으로인한탈리성
Selected Transdermal and Topical Drug Delivery Dosage Forms 2772
2773 A-2. TTS 의종류 1) Matrix diffusion Controlled transdermal delivery System ( 메트릭스확산제어경피약물전달체계 ) Metrix System 정해진표면적과두께를가지고있는 Polymer matrix 상에약물이균일하게분산되어있는형태로서약물의방출율은분산율에좌우된다 매트릭스확산제어경피약물전달체계 (a) 와방출패턴 (b) 의도식도 그약물
2774 2) Membrane moderated transdermal drug delivery system ( 분리막조절경피투과약물전달체계 ) Reservoir System 전달하고자하는약물및피부투과촉진제 (enhancer) 가담체 (Reservoir) 안에같이있고방출되는면쪽에분리막 (membra) 이있으며방출율은조성이나두께로조절한다. 분리막조절경피투과약물전달체계 (a) 와그약물방출패턴 (b) 의도식도
2775 Polymeric TTS 의비교 속도조절매개체 Matrix 형 약물저장층의 Polymer Reservoir 형 Rate-Controlling Membrane 방출속도 First Order zero Order 방출속도수단 Polymer Diffusion Membrane Diffusion 지속적속도조절어려움용이 제조용이어려움 Burst up 효과有無
2776 3) Mixed matrix membrane trasndermal drug delivery system ( 매트릭스 -분리막경피투여약물전달체계 ) Mixed matrix reservoir system 약물이균일하게분산되어있는 matrix 의방출면쪽에분리막이있다. 초기에는분리막에의해방출조절을하다가다음에는 matrix 에의해조절된다. 매트릭스 -분리막경피투여약물전달체계 (a) 와그약물방출율 (b) 의도식도
2777 4) Microsealed transdermal drug delivery system ( 미소봉합경피약물전달체계 ) 약물을유당 (lactose) 와같은분자량이작은미세입자에흡수시킨후 Silicone elastomer 에분산시키어수천개의미세약물을 elastomer matrix 내에저장시키어방출을조절한다 미소봉합경피약물전달체계의도식도
2778 5) Iontophoresis transdermal drug delivery system ( 이온영동경피투과약물전달체계 ) 전기로자극을주어약물을피부침투시키는방법 낮은전압으로지속적인전류 (0.025mA~1.2mA) 의흐름 6) 기타 1 Electroporation : 수백볼트 (100~200v) 의전기로피부각질층을확장시켜약물의전달을유도함 2 Electroosmosis : 약물의삼투압차이를발생시켜전달을증가시킴 3 Sonophoresis : 초음파를이용각질층을확장시켜약물의이동증가시킴 4 Lazersonophoresis : Lazer 를피부에조사하여각질층의진동을유발시켜피부의약물투과통과를확장시킴 5 수동적방법 : Pap 제
2779 Advanced TTS patches 1. Macroflux (ALZA) 2. E-TRANSE TRANS (Alza) Macroflux technology is designed E-TRANS electrotransport technology enables patient-
2780 3. Power Cosmetics Micro-electronic Cosmetic patch Thin and flexible micro-power source technology and device Micro-electric current and micro-stimulation Treat : age, wrinkle, dark spots, discoloration, whitening, firming, lifting, hydration, sliming, cellulite reduction 4. U-Strip U (Dermisonics( Dermisonics) The U-Strip Drug Delivery System generates ultrasonic transmissions of variable intensity and frequency, which are pulsed through a modified transdermal patch, acting to kinetically motivate the drug contained within the patch.
5. Others 2781
2782 Non-medicated Patches Nutrient(Face, Body, Nail) Skin Care(Therapeutic and Cosmetic) Breast up/enhancement Whitening (Face/Tooth) Anti-acne Anti-itching(Atopy) Weight Loss Depilatories Aroma Taning(Pad or Towel)
B. TTS 제형개발및제조공정 B-1. 경피흡수제제개발화공정 2783
Materials and Processing Technology Used in TTS and TDS 2784
2785 Formulation - 주요구성성분 - * 주성분 (Key Component, Drug) Ketoprofen, Piroxicam, Nicotine... * 용해제 (Solubilizer) Triacetin, Laticacid, Ethanol... * 투과촉진제 (Enhancer) Polyols, Fatty Acid, Amides * 습윤제 (Moisturizer) PG, 1,3 BG, Glycerol. Sorbitol * 항산화제 (Antioxidant) BHT, BHA, V E * 충진제 (Filler) ZnO, TiO 2, Baso 4, 전분 * 계면활성제 (Surfactant) Span, Tween, Brij * 점착제 (Adhesive) Solvent borne, Water borne, Hot melt
2786 약물의피부투과경로 신체의조직온도와등온선의분포도
2787 B-2. 경피흡수제제의구조및제조공정 1 구조지지체 (Backing film) - 피부에부착시제품을보호하는불투과성층약물저장층 (Drug resevior) - 약물의대부분을함유하는점착제층조절막 (Control membrane) - 약물이투과될때그흡수율을조절하는고분자막부착점착제층 (Contact adhesive) -7 일동안피부에부착하도록설계된저자극점착제층 (PSA : Pressure Sensitive Adhesive) 박리지 (Release liner) - 포장시제품을보호하는 film 으로서사용시제거함
2788 2 제조공정 flow ⅰ) Multilaminating process ⅱ) ) Form and seal process
2789 Coating System 1 Type of Coaters Manufacture of an adhesive dispersion-type TTS -
2 Type of Coating Line 2790 A Multicoating Line B Hybrid Coating Line (two chambers)
C Hybrid Coating Line (three chambers) 2791 D Returning Line - -