Jumat, 13 April 2018

Arco

Four strings have been attached
Tightly tuned on this pretty curve
They are covered by warm snow
Piled up by the river under the bridge

The core of melody doesn't need to be glued on the ground or tied to the anchor
It will find its own foothold and a way to reach the soul
Clouding your mind with all those old memories
By simply caress your heart with a million emotions

It seems like adding extra burden on the shoulder
But it's actually lift the heavy burden that dragged you down all this time
Washed away by mesmerizing strains
Soar from the deepest ravine of atlantis to the sun where Apollo awaits

The rhythm is not always beautiful like this
It used to walk on a street full of sharp gravels
It was faced by obstacle as big as a mountain
But it never look back

That's how it moves forward, putting one put in front of the other
Stroking up and down the hills, tirelessly
Even when it's really desperate sometimes, or most of the times
It keeps crawling on hands and knees

Because it's not easy to see the other side of shore
Just like it's not easy to turn the scratch of demon into song of an angel
But when you finally make the impossible possible
The voice of Arco, It's worth your while




Selasa, 26 Desember 2017

UJI DISOLUSI

UJI DISOLUSI TABLET & KAPSUL KONVENSIONAL

Disolusi mengukur persentase dari zat aktif yang dilepaskan dari tablet/kapsul dan telah dilarutkan dalam medium disolusi selama kondisi pengujian yang terkontrol dalam periode yang sudah ditetapkan.
- Tablet harus hancur terlebih dahulu,
- selanjutnya zat aktif bisa terlarut,
- waktu hancur lambat menandakan disolusi yang lambat,
- % disolusi zat aktif dipastikan dengan metode tervalidasi yang sesuai; UV/VIS, HPLC, AA, GC, dsb.


KLASIFIKASI PROFIL DISOLUSI SEDIAAN SOLID ORAL

- Very rapid release = ≥ 85% dalam ≤ 15 menit
- Rapidly dissolving =  ≥ 85% dalam ≤ 30 menit
- Immediate release = ≥ 75% dalam ≤ 45 menit


PENGAPLIKASIAN
  
Untuk pemilihan formula dalam tahap pengembangan
- Dengan membandingkan profil disolusi antara innovator dengan produk yang diformulasikan.
- Hint: Mulai dengan komparator untuk melihat profil disolusi dan waktu hancur pada tahap awal.
-  Merupakan strategi dasar R&D untuk memaksimalkan peluang saat uji bioekuivalensi.
Sebagai syarat data Uji Disolusi Terbanding untuk bio-batch dan innovator batch
- Batch yang sama dengan yang digunakan untuk uji bioekuivalensi.
- Mengajukan laporan dengan data, profil terbanding dan diskusi.
- Laporan ini akan menjadi bagian dari laporan Pharmaceutical Development.
- Penyertaan laporan yang sama saat uji bioekuivalensi juga direkomendasikan.
Menunjukkan bioekuivalensi in vivo satu atau lebih kekuatan sediaan yang lebih rendah dari FPP dapat di-biowaiver berdasarkan:
- Studi bioekuivalensi in vivo dari kekuatan sediaan tertinggi yang dapat diterima dibandingkan dengan produk komparator. 
- Menunjukkan F2 similarity profil disolusi.
- Jika kekuatan sediaan yang lebih rendah similar secara proporsional dalam formula ke dosis yang lebih tinggi (bio-batch) dan
- Jika semua persyaratan farmakokinetik memenuhi.
Perbandingan profil pelepasan dari batch-batch sangat penting
- Untuk menunjukkan similarity in vitro dari batch-batch tersebut.
- Menggarisbawahi bahwa studi bioekuivalensi biasanya hanya dilakukan sekali pada bio-batch selama pengembangan.
- Menunjukkan bahwa produk tersebut memiliki karakteristik disolusi yang sama saat upscale ke skala produksi.
- Studi harus disertakan dalam dossier sebagai bagian dari laporan pengembangan FPP.
Pemilihan spesifikasi disolusi untuk perilisan produk dan tujuan stabilita.
- Kondisi dan kriteria keberterimaan ditentukan.
- Profil disolusi dari bio-batch harus digunakan untuk tujuan ini.
- Spesifikasi disolusi harus dapat mendeteksi karakteristik pelepasan yang tidak sesuai dari batch komersial.
Aplikasi Perubahan Post-approval
- Penilaian perubahan formula untuk melihat bahwa profil dari batch yang berubah dan batch terkini masih similar.


FAKTOR-FAKTOR YANG MEMPENGARUHI DISOLUSI

- Karakteristik dari zat aktif seperti ukuran partikel, bentuk kristal dan bulk density.
- Komposisi produk seperti drug loading, identitaas, jenis dan jumlah excipients.
- Proses manufacturing seperti compression force dan peralatan.
- Efek dari kondisi penyimpanan seperti suhu dan kelembapan terhadap stabilitas.
 

 MEKANISME DISOLUSI

 Pembebasan solute atau obat dari matrix formula (disintegrasi)
- Sifat kohesif dari bentuk sediaan solid yang diformulasikan memegang peranan penting dalam disintegrasi dan erosi,
- Untuk formulasi semi-solid atau cair, dispersi lipid atau partitioning obat dari fase lipid memegang peranan penting,
-  Jika pada tahap pertama disolusi lajunya dihambat maka laju disolusi tersebut diperkirakan sebagai disintegration controlled.
 Disolusi (solubilisasi partikel obat) dalam medium cair 
- Solubilisasi partikel obat tergantung pada sifat physicochemical dari obat seperti bentuk kimia (salt, free acid, free base) dan atribut fisikanya.


PEMILIHAN MEDIUM

Untuk kualitas batch to batch, pemilihan medium uji bisa berdasarkan data solubilitas dan rentang dosis dari produk obat untuk menjamin sink condition terpenuhi. Istilah sink condition didefinisikan sebagai volume medium setidaknya 3 kali lebih besar dari yang dipersyaratkan untuk membentuk larutan tersaturasi dari bahan obat. Ketika uji disolusi ditujukan untuk mengindikasikan sifat biopharmaceutical, Simulasikan secara dekat lingkungan dalam GIT dari sink condition. Pertama-tama, evaluasi menggunakan media dalam rentang pH physiologic dari 1,2 sampai 6,8 (1,2 sampai 7,5 untuk modified release).

PEMILIHAN APPARATUS

Dijabarkan dalam USP di bawah General Chapters of Dissolution and drug Release.





Paralyzed

Struck by lightning wouldn't even close to this sensation
Of dragged down to the bottom of the red lake, surrounded by cold flesh
A warrior surges, a warrior falls, a warrior trembles
But no warrior runs, because there is no place to hide

A mermaid in the middle of a wishful fountain gather hopes from yearned souls
Desperate to walk off the stage
But the show keeps on going and the curtain can't be closed
Life must go on

It's such a shame that life is not a slut
It is not cheap either
Air might be free but it needs an enormous sum of struggle just to breathe
The music keeps on playing but there is no guarantee for this tiny heartbeat

Chaos everywhere
Screaming comes from every direction
Smokes and fire as far as the eye can see
But the body stand still

Suddenly the ground has a strong electromagnetic power
And the air smothering so tight
All terrors inside burst out until no more left
Leaving a paralyzed vessel of blankness



Senin, 25 Desember 2017

A New Beginning

Rays of twilight rain on me
Pouring such a warm feeling that melts the ice inside
Veil of the night wraps me under the stars
Caressing composedly with its fragile touch

Stuck on a deserted island with a chest full of treasure
No food, no roof, no companion
Just gold and diamonds
Wait for this cycle to end so a new beginning can be started

Go to another land where there is no limitation to possibility except for infinity
Arrive at Neverland and make it a wonderland
Close the eyes and dream
Of me, Of you, Of us

Jumat, 18 November 2016

TABLETTING PROBLEMS & POSSIBLE CURE

In tabletting, it’s unavoidable to have one or a few problems but those problems can be cured with certain ways. Below are problems in tablet finished product along with their possible causes and cures:
PROBLEM
POSSIBLE CAUSE
CURE
Inconsistent Weight
Variation in punch length (lower)
Replace or regrind to length
Inconsistent granule
Improve granule / mixing technique
Empty feed frame
Check hopper / feeder, ensure granule flows freely
Punch holding plugs
Replace
Dirt under weight adjustment ramp
Remove ramp, clean
Incorrect setting of feeder paddle speed
Adjust as required
Incorrect setting of feeder inlet bowl
Adjust as required
Tablet stick to upper punch
Damaged upper punch
Refurbish or replace punches
High moisture level in granule
Dry granules in oven or F.B.D., sieve and lubricate
Lack of, or insufficient lubricant
Add or increase lubricate
Double impression
Worm punch holding pads
Replace
Excessive tamping force
Increase tablet thickness
Flash' on tablet edge
Worm punch or die
If possible reverse die or replaace badly won punches
If tapered dies are being used tablet compressed in taperd section of die
Increase upper punch penetration
Variation in thickness / hardness
Worn pressure roll
Replace
Variation in upper or lower punch lengths
Replace or regrind to length
Inconsistent granule
Improve granule
Overload pressure, setting set too close to tabletting pressure
Reset
Safety overload pressure release operating
Damaged punches (burr on tip)
Refurbish or replace
Excessive pressure
Reduce pressure, i.e. increase tablet thickness or reduce fill
Overload set to close to tabletting pressure
Reset overload
Lower punch
Mtl stuck to punch or die
Check for worn punches and dies
High moisture level in granules
Dry granules in oven or F.B.D., sieve and lubricate
Top of tablet is split / cracked
Damaged punches
Refurbish or replace
Granules maybe too dry
Add moisture, remix, granulate, lubricate
Tablets breaking on take off
Take off plate incorrectly set
Check and reset
Lower punch ejection
Check and reset
Insufficient load at compression point
Increase pressure, check overload
Speed too high for particular material
Reduce speed until acceptable  tablet is obtained
Not enough binder
Increase
Granules too dry
Increase moisture level
Insufficient feed to dies (soft tablets)
Check hopper and flow of material
Feeder height incorrectly set
Check and reset
Tablets binding in die
Worn dies
Reverse or replace
High moisture level in granule
Dry, sieve and lubricate or reduce fill
Lack of, or insufficient lubricant
Increase
Tablets split in half (lamination)
Take off plate incorrectly set
Check and reset
Lower punch ejection incorrectly set
Check and reset
Speed too high
Reduce speed
Insufficient feed to die
Check hopper and flow of material
Worn / damaged punches
Refurbish or replace
High moisture level in granules
Dry in oven or F.B.D., sieve and relubricate
Not enough binder in mix
Increase
Excessive pressure
Increase tablet thickness
Granules too dry
Increase moisture level
Burr or punch tips
Refurbish or replace
Feeder height incorrectly set
Check and reset
Loss of material
Feed frame / pedestal height incorrectly set
Check and reset
Upper punch penetration set too high
Check and reset
Worn lower punches or dies
Replace
Tail over die / scraper set / worn
Check, reset or replace
Recirculating channel worn or missing
Replace
Indequate dust control unit
Overhaul or replace
Excessive flow of material to feed frame
Reduce flow

The cures that have been explained are merely a guide because there are many cures that can also solve the same problem/s. One of the most critical parameters that has to be assured is how to make a proper mass that will suit the specification of the finished product the best.

Arco

Four strings have been attached Tightly tuned on this pretty curve They are covered by warm snow Piled up by the river under the bridge ...