METODE PEMBUATAN TABLET -...
Transcript of METODE PEMBUATAN TABLET -...
METODE PEMBUATAN TABLET
SUTRIYO
METHODS OF PREPARATION
MOLDING
DIRECT COMPRESSION
DRY GRANULATION
WET GRANULATION
SELECTION OF METHODS
STABILITY CHARACTERISTICS OF THE DRUG
HUMIDITY TEMPERATURE
STABLE UNSTABLE
DIRECT COMPRESSION
DRY GRANULATION
WET GRANULATION
WET GRANULATION
DIRECT COMPRESSION
DRY GRANULATION
Dose of Drug
High Dose
(> 250 mg)
Most of the tablet will
be drug
a. compressibility
b. flowability
Low Dose
(< 25 mg)
Most of the tablet will be
excipients
Content uniformity problem
PROPERTIES OF BULK
BULK PROPERTIES
DIRECT COMPRESSION
DRY GRANULATION
WET GRANULATION
COMPRESSIBILITY GOOD GOOD NONE
FLOWABILITY GOOD NONE NONE
DIRECT COMPRESSION
the process by which tablets are compressed directly from powder blends of the active ingredient and suitable excipients (including fillers, disintegrants, and lubricants), which will flow uniformly into a die cavity and form into a firm compact.
No pretreatment of the powder blends by wet or dry granulation procedures
Advantages 1. More economical :
– reduced processing time – reduced labor costs – fewer manufacturing steps – Fewer pieces of equipment, – less process validation – lower consumption of power
2. without the need for moisture and heat which is inherent in most wet granulation procedures and the avoidance of high compaction pressures involved in producing tablets by slugging or roll compaction
3. optimization of tablet disintegration (disintegrant is able to perform optimally)
4. fewer chemical stability problems would be encountered in tablets prepared by direct compression
5. Useful for crystalline drugs, large dose drugs, or drugs that are moisture sensitive
6. Limited number of excipients - optimal bioavailability
Disadvantages
Requires materials that can be directly compressed
Drugs/Excipients must have good flow properties
Can get non-uniform tablets
PROCESS
MILLING OF DRUGS AND EXCIPIENTS
MIXING OF INGREDIENTS
TABLET COMPRESSION
Direct Compression
drug, filler, internal
disintegrant
bulk
milling mixing
compression tablet evaluation
ballmill V-Blend
GRANULATION
• proses aglomerasi atau pembesaran ukuran partikel dari partikel kecil menjadi aglomerat yang secara fisik lebih besar dan lebih kuat sedangkan partikel asal masih dapat diidentifikasi
• Proses granulasi adalah setiap proses dimana partikel kecil berkumpul menjadi lebih besar, dengan massa yang permanen, dimana partikel asal masih dapat diidentifikasi. (Perry’s Chemical Engineer’s Handbook)
• ….. terbentuknya suatu kelompok (clusters) dari serbuk atau campuran serbuk dan pengikat untuk menghasilkan material yang kohesif dan bebas mengalir yang selanjutnya dapat diproses dengan kompresi atau enkapsulasi.
TUJUAN GRANULASI
1. meningkatkan ukuran partikel
2. meningkatkan sifat aliran (flowability)
3. meningkatkan kompresibilitas (compressibility)
4. mengecilkan volume (densification)
5. menghasilkan partikel yang lebih sferis dan seragam
6. menghasilkan permukaan yang hidrofilik
7. mendistribusikan bahan aktif
PROSES DAN METODE
Proses Metode
Granulasi basah Wet massing
Fluid Bed Granulation
Spray Drying
Pan Granulation
Extrusion and Pelletizing
Granulasi Kering Roller Compaction
Slugging
DRY GRANULATION
• Dry granulation or Slugging - process of preparing a tablet mixture without a wet binder or moisture.
• A slug is formed and then compressed
• Advantages
– Useful for water and heat sensitive drugs
– Fewer steps
• Disadvantages
– Requires drugs or excipients with cohesive properties
DRY GRANULATION
MILLING OF DRUGS AND EXCIPIENTS
MIXING OF MILLED POWDER
COMPRESSION INTO LARGE, HARD TABLETS (SLUGS)
SCREENING OF SLUGS ..... GRANULE
MIXING WITH LUBRICANT AND EXTERNAL DISINTEGRANT
TABLET COMPRESSION
drug, filler,
internal
disintegrant
bulk
milling mixing slugging crushing
compression tablet evaluation mixing sifting
ballmill V-Blend
chilsonator
V-Blend
Lubricant &
External disintegrat
SLUGING/COMPACTOR
DRY GRANULATOR
V-BLEND
Oscilating granulator
Double cone mixer V-Blend
WET GRANULATION
a. wet massing of a tablet powder mixture with liquid adhesives followed by wet screening or granulation
b. Advantages
Most reliable
Highest probability of meeting the requirements for making a successful tablet
c. Disadvantages
– Need to prepare a uniform granulation
– Labor Intensive
– Time Consuming
– Can not use for water and heat sensitive drugs
WET GRANULATION
1. Milling of Drugs And Excipients
2. Mixing of Milled Powder
3. Preparation of Binder Solution
4. Mixing Binder Solution With Powder Mixture to Form Wet Mass (Kneading)
5. Coarse Screening of Wet Mass using 6-12 Mesh
6. Drying Moist Granules (Indikator : MC = 2,5 – 5 %)
7. Screening Dry Granules using 14-20 Mesh
8. Mixing Screened Granules with Lubricant and External Disintegrant
9. Tablet Compression
Stages involved in granulation (Newitt , Conway-Jones dan Barlow )
compression tablet evaluasi Final mixing Sifting 2
Lubricant &
External disintegrat
drying
Fluid Bed
Dryer
drug, filler,
internal
disintegrant
bulk milling premixing
Sifting 1 wetmixing
Binder solution
ballmill V-Blend Planetary
Mixer
SCREENING DRY GRANULES
Diameter Tablet
(inchi)
Diameter Tablet
(mm)
Ayakan (mesh)
6/32 5 20
7/32 – 9/32 5,5 – 7
16
10/32 – 13/32
8 – 10 14
≥ 14/32 ≥ 11 12
METODE PEMBUATAN DIRECT
COMPRESSION DRY GRANULATION WET GRANULATION
1. MILLING OF DRUGS AND EXCIPIENTS
2. MIXING OF INGREDIENTS
3. TABLET COMPRESSION
1. MILLING OF DRUGS AND EXCIPIENTS
2. MIXING OF MILLED POWDER
3. COMPRESSION INTO LARGE, HARD TABLETS (SLUGS)
4. SCREENING OF SLUGS
5. MIXING WITH LUBRICANT AND EXTERNAL DISINTEGRATOR
6. TABLET COMPRESSION
1. MILLING OF DRUGS AND EXCIPIENTS
2. MIXING OF MILLED POWDER
3. PREPARATION OF BINDER SOLUTION
4. MIXING BINDER SOLUTION WITH POWDER MIXTURE TO FORM WET MASS (KNEADING)
5. COARSE SCREENING OF WET MASS USING 6-12 MESH
6. DRYING MOIST GRANULES (indikator : MC = 2,5 – 5 %)
7. SCREENING DRY GRANULES USING 14-20 MESH
8. MIXING SCREENED GRANULES WITH LUBRICANT AND EXTERNAL DISINTEGRATOR
9. TABLET COMPRESSION
HIGH SHEAR GRANULATOR
PLANETARY MIXER
LOW SHEAR GRANULATOR
RIBBON BLENDER
ORBITING SCREW MIXER TWIN-SHELL BLENDER
ZIG-ZAG MIXER AGGLOMERATOR
BATCH FLUID BED GRANULATOR
Pencampuran kering (dry blend)
Mekanisme utama dry blending
• diffusion (difusi)
• convection (konveksi)
• shear (mencukur)
Diffusion
redistribusi partikel dengan gerakan acak dari partikel satu ke partikel yang lain.
convection gerakan dari kelompok partikel yang berdekatan dari
satu tempat ke tempat yang lain dalam campuran.
Shear perubahan dalam konfigurasi bahan melalui
pembentukan bidang yang menggelincir (slip) dalam campuran
Pencampuran padat (solid mixing)
Pencampuran Cair-Padat (Liquid-Solid Mixing): kneading
• Agglomerasi (agglomeration)
• Pemecahan agglomerasi (agglomeration breakdown)
• Agglomerasi kembali (Re-agglomeration)
• Pembentukan Pasta (Paste Formation)
Agglomerasi (agglomeration)
• Tetesan pelarut seperti air atau alkohol atau larutan pengikat, berkontak dan melekat pada partikel serbuk yang bergerak, dan membuat lingkaran di sekelilingnya.
• Partikel serbuk terbasahi oleh cairan, cairan bermigrasi melalui aksi kapiler (pendular dan/atau funicular) menjadi celah partikel-partikel dan membentuk agglomerat serbuk–cair yang besar.
• Melekatnya partikel ke partikel lain membentuk suatu agglomerat dengan ukuran diameter 1 – 5 cm atau lebih besar.
Pemecahan agglomerasi (agglomeration breakdown)
• Setelah fase awal pembentukan agglomerat yang besar, forsa shear dan forsa pencampuran mulai memecah agglomerat.
• Dalam fase ini, cairan dibawa melalui campuran, melewati agglomerat yang lebih kecil yang terus menerus mengurangi ukuran.
• Berkurangnya cairan pada permukaan partikel menyebabkan terjadinya pemecahan aglomerat
Agglomerasi kembali (Re-agglomeration)
• Partikel saling berkontak membentuk jembatan akibat adanya larutan pengikat atau bahan yang terlarut
Pembentukan Pasta (Paste Formation)
• Jika pencampuran dilanjutkan setelah titik akhir granulasi yang normal tercapai (yang berbeda untuk tiap formula), suatu massa basah yang kental yang menyerupai pasta mulai terbentuk sebagai hasil dari solubilisasi, solvasi dan sebagainya.
• Pasta ini, akan sulit untuk dikeringkan dan jika kering menjadi granul yang sangat keras yang sulit untuk digiling (milling) dan dalam banyak kasus menunjukkan compaction yang jelek dalam mesin tablet
DIRECT COMPRESSION
DRY GRANULATION WET GRANULATION
1. MILLING OF DRUGS AND EXCIPIENTS
2. MIXING OF INGREDIENTS
3. TABLET COMPRESSION
1. MILLING OF DRUGS AND EXCIPIENTS
2. MIXING OF MILLED POWDER
3. COMPRESSION INTO LARGE, HARD TABLETS (SLUGS)
4. SCREENING OF SLUGS
5. MIXING WITH LUBRICANT AND EXTERNAL DISINTEGRATOR
6. TABLET COMPRESSION
1. MILLING OF DRUGS AND EXCIPIENTS
2. MIXING OF MILLED POWDER
3. PREPARATION OF BINDER SOLUTION
4. MIXING BINDER SOLUTION WITH POWDER MIXTURE TO FORM WET MASS (KNEADING)
5. COARSE SCREENING OF WET MASS USING 6-12 MESH
6. DRYING MOIST GRANULES (indikator : MC = 2,5 – 5 %)
7. SCREENING DRY GRANULES USING 14-20 MESH
8. MIXING SCREENED GRANULES WITH LUBRICANT AND EXTERNAL DISINTEGRATOR
9. TABLET COMPRESSION