New alfentanil composition for treatment of acute pain
A technology of composition and mixture, applied in directions such as drug combination, non-central analgesic, drug delivery, etc., can solve the problems such as short-term or long-term stability of alfentanil solution that are not reported
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Embodiment 1
[0123] Alfentanil Sublingual Tablets - Granulated Carrier Particles
[0124] (a) carrier particle
[0125] (i) is composed of anhydrous citric acid (fine grain 16 / 40 grade, DSM, Basel, Switzerland) and mannitol (Pearlitol TM 400DC, Roquette, Lestrem, France) eight batches of carrier particles (for tablet batches 1 to 8 as identified in Tables 1 and 2 below) were prepared. Carrier particles were prepared as follows.
[0126] Grind the citric acid by hand using a pestle and mortar, then pass through a sieve. A fraction with a particle size between 90 μm and 180 μm is used in the granulation. First, follow the amounts below:
[0127] (i) 0.2502g citric acid and 199.8g mannitol;
[0128] (ii) 1.2524g citric acid and 198.8g mannitol; and
[0129] (iii) 2.5109g citric acid and 197.5g mannitol;
[0130] The citric acid and mannitol were dry mixed for about 1 minute in a small size intensive mixer (Braun electronic 4261, Braun AG, Germany).
[0131] These amounts were chosen...
Embodiment 2
[0152] Alfentanil Sublingual Tablets
Embodiment 21
[0153] Example 2.1 - Batches of Granulated Carrier Particles
[0154] (a) Prepared as follows containing anhydrous citric acid (fine particle grade 16 / 40, DSM, Basel, Switzerland) or trisodium citrate dihydrate (Citrique Belge, Belgium) and mannitol (Pearlitol TM 400DC, Roquette, Lestrem, France) granulated carrier particles.
[0155] First, citric acid and sodium citrate were milled using an air jet mill (Pilotmill-1; Food and Pharma Systems, Italy). Citric acid was milled to volume-based particle sizes (D(4,3)) of 4.3 μm and 99 μm, and sodium citrate was milled to particle sizes of 9.6 μm, 21 μm and 94 μm.
[0156] First, take the following amounts:
[0157] (i) 0.125g citric acid / citrate and 99.875g mannitol for a 100g batch (or 0.25g citric acid and 199.75g mannitol for a 200g batch); and
[0158] (ii) 2.502g citric acid and 97.498g mannitol for a 100g batch (or 5.004g citric acid and 194.996g mannitol for a 200g batch).
[0159] The citric acid / citrate and mannitol we...
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