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¿µÁøÄÚÆÛ·¹ÀÌ¼Ç Á¾ÇÕÄ«´Ù·Î±× |
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Introduction
Expxcipients (ºÎÇüÁ¦(Ý·û¡ð¥), º¸Çü¾à(ÜÍû¡å·)) ·Î »ç¿ëµÇ´Â ¹°ÁúÀÇ ºÐ¸» Ư¼ºÀº Á¦Á¦ °øÁ¤°ú Ç°Áú¿¡ Áß¿äÇÑ ¿µÇâÀ» ¹ÌĨ´Ï´Ù.
Á¤Á¦ ó¹æÀÇ ºÎÇüÁ¦¸¦ ¼±ÅÃÇÏ´Â µ¥ ÀÖ¾î, ºÎÇüÁ¦ÀÇ ºÐ¸» ¿¬±¸ ÁöÇ¥¸¦ ÃøÁ¤ÇÔÀ¸·Î½á ó¹æ°ú °øÁ¤ ¼³°è¸¦ ±âÁ¸ÀÇ '°æÇè'¿¡ ÀÇÁ¸ÇÏ´Â °Í¿¡¼
°úÇÐÀûÀÌ°í Á¤·®ÀûÀÎ ¼öÁØÀ¸·Î ¹ßÀü½Ãų ¼ö ÀÖ½À´Ï´Ù. µ¿½Ã¿¡ ºÎÇüÁ¦ÀÇ Á¤·®Àû °ü¸®´Â Á¤Á¦ÀÇ Ç°Áú°ú ¾ÈÁ¤¼ºÀ» º¸ÀåÇÏ´Â µ¥µµ µµ¿òÀÌ µË´Ï´Ù.
Lactose (À¯´ç) ´Â °¡Àå ÀϹÝÀûÀÎ Á¤Á¦ ºÎÇüÁ¦ Áß ÇϳªÀÔ´Ï´Ù. USP (United States Pharmacopeia, ¹Ì±¹¾àÀü, Ú¸ÏÐå·îð) ´Â ·¹ÀÌÀú ȸÀý¹ý¿¡ ÀÇÇÑ ¿ø·á ÀÔÀÚ Å©±â ÃøÁ¤¿¡ ´ëÇØ,
±â±¸ÀÇ ±¸Á¶¿Í ¿ø¸®, °Ç½Ä ¹× ½À½Ä ºÐ»êÀÇ ±¸Ã¼ÀûÀÎ ¹æ¹ý, ÃøÁ¤ °úÁ¤¿¡¼ÀÇ ¿äÀÎ µî ¸íÈ®ÇÑ ±ÔÁ¤À» °¡Áö°í ÀÖ½À´Ï´Ù.
±×·¯³ª ƯÁ¤ À¯´ç¿¡ ´ëÇؼ´Â ºÐ»ê ¾Ð·ÂÀ» ¼±ÅÃÇÏ´Â ¹æ¹ýÀ̳ª °Ç½Ä ¹× ½À½Ä ¹æ¹ýÀÇ °á°ú¸¦ Æò°¡ÇÏ´Â ¹æ¹ý¿¡ ´ëÇÑ °ü·Ã ÁöħÀÌ ¾ø½À´Ï´Ù.
º» ³í¹®¿¡¼´Â USP ¿Í ISO 13320 ¿¡ µû¶ó À¯´ç ÀÔÀÚ Å©±â ºÐÆ÷ ÃøÁ¤¿¡ ´ëÇÑ Ã¼°èÀûÀÎ ¿¬±¸¸¦ ¼öÇàÇÏ¿´½À´Ï´Ù.
1. Experiment
1.1 Instruments
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Bettersizer 2600 laser particle size analyzer from Bettersize Instrument Ltd; |
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MS303S electronic scale from Mettler Toledo; |
1.2 Sample and reagent
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No.1 : non-micronized lactose sample (batch No.00116-17); |
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No.2 : micronized lactose sample. |
2. Particle size distribution measurement and method evaluation
2.1 Study on the methodology of dry dispersion method
Dry Dispersion Àº ¾ÐÃà °ø±â¸¦ ÀÌ¿ëÇÏ¿© ºÐ¸» ÀÔÀÚ¸¦ ¿î¹ÝÇÏ°í, ÀÔÀÚ¿Í ÀÔÀÚÀÇ Ãæµ¹, ÀÔÀÚ¿Í ÆÄÀÌÇÁÀÇ Ãæµ¹, ±×¸®°í °ø±â È帧ÀÇ Àü´Ü¿¡ ÀÇÇØ ºÐ¸» ÀÔÀÚ¸¦ ºÐ»ê½ÃÅ°´Â ¹æ¹ýÀÔ´Ï´Ù.
Lactose Powder ´Â ÀÛÀº À¯±â ºÐÀÚ ÀÔÀÚ·Î ±¸¼ºµÇ¾î ÀÖÀ¸¸ç, ÀÌ·¯ÇÑ ÀÔÀÚ´Â Shear Stress ¿Í Collision (Àü´Ü ÀÀ·Â°ú Ãæµ¹) ¿¡ ÀÇÇØ ÆÄ¼ÕµÉ ¼ö ÀÖ½À´Ï´Ù. ¿ø·¡ ÀÔÀÚ¸¦ ÆļսÃÅ°Áö ¾ÊÀ¸¸é¼ Å« ÀÀÁýü¸¦ ºÐ»ê½ÃÅ°±â À§ÇØ,
USP (¹Ì±¹ ¾àÀü) ¿¡¼´Â ´Ù¾çÇÑ Dispersion Intensity (ºÐ»ê°µµ) °¡ ÃøÁ¤ °á°ú¿¡ ¹ÌÄ¡´Â ¿µÇâÀ» Á¶»çÇÒ °ÍÀ» ¿ä±¸ÇÏ°í ÀÖ½À´Ï´Ù (USP 429).
°Ç½Ä ºÐ»ê ½ÇÇè¿¡¼ ºÐ»ê ¾Ð·ÂÀÌ ÀÔÀÚ Å©±â ÃøÁ¤ °á°ú¿¡ ¹ÌÄ¡´Â ¿µÇâÀ» Á¶»çÇß½À´Ï´Ù. ºÐ»ê ¾Ð·ÂÀº 0.05 MPa¿¡¼ 4 MPa±îÁö ¹üÀ§·Î ¼³Á¤ÇÏ¿´À¸¸ç, 0.05 MPa¿¡¼ 0.1 MPa¸¶´Ù µ¥ÀÌÅ͸¦ ÃøÁ¤Çß½À´Ï´Ù.
°¡·ÎÃà : ºÐ»ê ¾Ð·Â;   ¼¼·ÎÃà : ÀÔÀÚ Å©±â;   ÆĶõ °î¼± : D10;   ÁÖȲ °î¼± : D50;   ȸ»ö °î¼±: D90.
Figure 1. Particle size pressure titration data of No.2 micronized lactose sample
ÀÌ»óÀûÀÎ ¾Ð·Â ÀûÁ¤ °î¼±¿¡¼´Â ºÐ»ê ¾Ð·ÂÀÌ Áõ°¡ÇÔ¿¡ µû¶ó ÀÔÀÚ Å©±â°¡ Á¡Â÷ °¨¼ÒÇÏ°í, °î¼±Àº Á¡Â÷ ¾ÈÁ¤ÀûÀÎ ±¸°£¿¡ µµ´ÞÇÕ´Ï´Ù.
¾Ð·ÂÀÌ ´õ Áõ°¡ÇÏ¸é °î¼±ÀÌ ´õ ¾Æ·¡·Î ³»·Á°¡¸ç, ÀÌ´Â Å« ÀÀÁýü°¡ Á¡Â÷ ´ÜÀÏ ÀÔÀÚ·Î ºÐ»êµÇ´Â °ÍÀ» ÀǹÌÇÕ´Ï´Ù.
±×·¯³ª ¾Ð·ÂÀ» ´õ Áõ°¡½ÃÅ°¸é ¾à¹° ÀÔÀÚ°¡ ÆÄ¼ÕµÉ ¼ö ÀÖ½À´Ï´Ù.
À§ÀÇ ¾Ð·Â ÀûÁ¤ °î¼±À» ÅëÇØ, À¯´ç »ùÇÃÀº 0.1 MPa ¿¡¼ 0.2 MPa »çÀÌ¿¡¼ ¸íÈ®ÇÑ '¾ÈÁ¤Àû ±¸°£'À» ³ªÅ¸³Â½À´Ï´Ù.
Ãß°¡ÀûÀÎ ºÐ¼®À» À§ÇØ, ¹ÌÅ©·ÐÈµÈ À¯´ç »ùÇÃÀÇ À̹ÌÁö¸¦ ĸóÇß½À´Ï´Ù (Figure 2 ¹× 3).
ÀÌ À̹ÌÁö¿¡¼´Â »ùÇÃÀÌ ¹ÝÅõ¸íÇÑ ºÒ±ÔÄ¢ °áÁ¤ ÀÔÀÚ·Î ³ªÅ¸³µ½À´Ï´Ù.
»ùÇÃÀÇ »óŸ¦ ÆÇ´ÜÇØ º¸¾ÒÀ» ¶§, ÀÌ »ùÇÃÀº ½±°Ô ÆÄ¼ÕµÉ ¼ö ÀÖ´Â °ÍÀ¸·Î º¸¿´½À´Ï´Ù. °Ç½Ä ºÐ»ê ¾Ð·ÂÀ» Áõ°¡½ÃÅ°¸é ÀÔÀÚ ÆļÕÀÇ À§Çèµµ ±×¿¡ µû¶ó Áõ°¡ÇÒ °ÍÀÔ´Ï´Ù.
Figure 2. Particle image of No.2 micronized lactose sample
Figure 3. Particle image of No.2 micronized lactose sample
2.2 Research of the precision of dry dispersion method
À¯´çÀÇ Ãë¾àÇÑ Æ¯¼ºÀ» °í·ÁÇÏ¿©, 0.1 MPa ÀÇ ºÐ»ê ¾Ð·Â ÇÏ¿¡¼ »ùÇà ũ±âÀÇ Á¤¹Ðµµ°¡ Á¶»çµÇ¾ú½À´Ï´Ù.
Figure 4 ¿Í 5 ´Â p-micronized ¹× micronized sample ÀÇ ÀÔÀÚ Å©±â ºÐÆ÷ °î¼±°ú ÀçÇö¼º µ¥ÀÌÅ͸¦ º¸¿©ÁÝ´Ï´Ù.
µÎ »ùÇÃÀÇ °á°ú ÀçÇö¼º °á°ú´Â USP ¿ä±¸ »çÇ×À» ÈξÀ ÃÊ°úÇßÀ¸¸ç, D50 µ¥ÀÌÅÍÀÇ º¯µ¿Àº 0.5% ¹Ì¸¸À̾ú°í D10 ¹× D90 µ¥ÀÌÅÍÀÇ »ó´ë Ç¥ÁØ ÆíÂ÷´Â 1% ¹Ì¸¸ÀÌ¾î¼ °Ç½Ä ºÐ»ê¹ýÀÇ ³ôÀº Á¤È®¼ºÀ» ³ªÅ¸³Â½À´Ï´Ù.
Figure 4. Particle size distribution and RSD of non- micronized lactose sample (dry dispersion)
Figure 5. Particle size distribution and RSD of micronized lactose sample (dry dispersion)
3. Conclusion
Dry Dispersion Àº À¯´çÀÇ ÀÔÀÚ Å©±â ºÐÆ÷¸¦ ÃøÁ¤ÇÏ´Â ÀûÇÕÇÑ ¹æ¹ýÀÔ´Ï´Ù. ±×·¯³ª À¯´çÀÇ Ãë¾à¼ºÀ» °í·ÁÇÒ ¶§, À¯´ç ¿øÀÔÀÚÀÇ ÆļÕÀ» ¹æÁöÇϱâ À§ÇØ ½ÃÇè ¾Ð·ÂÀº °¡´ÉÇÑ ÇÑ ÀÛ¾Æ¾ß ÇÕ´Ï´Ù.
À§ ½ÇÇè¿¡¼´Â 0.1 MPa¸¦ ¼±ÅÃÇÏ¿© ¸¸Á·½º·¯¿î °á°ú¸¦ ¾ò¾ú½À´Ï´Ù.
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