Amorphous drugs and amorphization
Why amorphous drugs PDF Print E-mail

Why obtaining a new drug amorphous form


The amorphous solid state possesses several advantages in comparison to the crystalline state which allow enhanced forms of drugs to be produced. Many drugs when generated as an amorphous form will exhibit one or more of the following:


Solubility

The amorphous state is thermodynamically the form with the highest solubility. Consequently, amorphous forms will exhibit a greater solubility in a solvent than any crystalline form. Solubility advantages of factors >1000 have been observed between crystalline and amorphous drugs. The increased solubility of amorphous actives can lead to dramatically increased intrinsic dissolution rates when compared to crystalline forms.
Activery offers the production of stable amorphous microparticles which show significantly enhanced solubility when compared to a crystalline reference.

 

Wettability

For a drug to dissolve, its surface has first to be wetted by the surrounding fluid. Amorphous forms possess a chemically randomized surface which expresses equal amounts of hydrophobic and hydrophilic interactions which can lead to improved wettability expressed by a lower contact angle a of the drug particle surface with a liquid. A lower contact angle represents a higher degree of hydrophily with consequently faster surface wetting and faster dissolution.
Activery offers the generation of amorphous powders which show enhanced wetting through lower contact angles when compared to a crystalline starting material.

 

 
Leading drugs and its solid form (amorphous and crystalline) PDF Print E-mail
Brand Name(s)
Generic Name
Solid state
Sales 2006 (USD millions)
Change from 2005
Company(ies)
Disease/Medical Use
Lipitor
Atorvastatin
Non amorphous
14,385
7%
Pfizer, Astellas Pharma
Cholesterol
Advair, Seretide
Fluticasone + Salmeterol
Non amorphous
6,129
12%
GlaxoSmithKline
Asthma
Plavix, Iscover
Clopidogrel
Crystalline material
6,057
-5%
Bristol-Myers Squibb, Sanofi-Aventis
Thrombotic events
Nexium
Esomeprazole
Crystalline
5,182
12%
AstraZeneca
Gastrointestinal disorders
Norvasc
Amlodipine
Crystalline
4,866
3%
Pfizer
Hypertension
Remicade
Infliximab
Amorphous
4,428
23%
Johnson & Johnson, Schering-Plough, Tanabe
Rheumatoid arthritis
Enbrel
Etanercept
Amorphous
4,379
20%
Amgen, Wyeth
Rheumatoid arthritis
Zyprexa
Olanzapine
4,364
4%
Eli Lilly
Schizophrenia
Diovan
Valsartan
Amorphous drug
4,223
15%
Novartis
Hypertension
Risperdal
Risperidone
4,183
18%
Johnson & Johnson
Schizophrenia
Aranesp
Darbepoetin alfa
Amorphous
4,121
26%
Amgen
Anemia
Rituxan, MabThera
Rituximab
Amorphous
3,861
16%
Roche, Genentech, Biogen Idec, Chugai Pharmaceutical
Non-Hodgkin’s lymphoma
Effexor
Venlafaxine
Crystalline
3,722
8%
Wyeth
Depression, Anxiety disorders
Protonix, Pantozol, Pantoloc
Pantoprazole
Crystalline
3,621
4%
Wyeth, Altana, Solvay
Gastrointestinal disorders
Singulair
Montelukast
Crystalline
3,579
20%
Merck & Co.
Asthma
Seroquel
Quetiapine
Crystalline
3,560
23%
AstraZeneca, Astellas Pharma
Schizophrenia
Prevacid, Takepron
Lansoprazole
Crystalline
3,425
3%
TAP Pharmaceuticals, Takeda Pharmaceutical
Gastrointestinal disorders
Procrit, Eprex
Erythropoietin
Amorphous drug
3,180
-4%
Johnson & Johnson
Anemia
Cozaar, Hyzaar
Losartan
3,163
4%
Merck & Co.
Hypertension
Fosamax
Alendronate
3,134
-2%
Merck & Co.
Osteoporosis
Herceptin
Trastuzumab
Amorphous
3,134
83%
Roche, Genentech, Chugai Pharmaceutical
Breast cancer
Lovenox, Clexane
Enoxaparin
Amorphous
3,059
14%
Sanofi-Aventis
Deep-vein thrombosis
Avandia, Avandamet, Avandaryl
Rosiglitazone
Crystalline
3,043
26%
GlaxoSmithKline
Type 2 diabetes
Actos
Pioglitazone
Crystalline
2,880
25%
Takeda Pharmaceutical, Eli Lilly
Type 2 diabetes
Zocor
Simvastatin
Crystalline
2,803
-36%
Merck & Co.
Cholesterol
Copaxone
Glatiramer
Amorphous
2,757
19%
Teva Pharmaceutical Industries, Sanofi-Aventis
Multiple sclerosis
AcipHex, Pariet
Rabeprazole
Crystalline
2,729
-4%
Eisai, Johnson & Johnson
Gastrointestinal disorders
Neulasta
Filgrastim
Amorphous
2,710
18%
Amgen
Neutropenia
Lexapro, Cipralex
Escitalopram
Crystalline
2,696
16%
Forest Laboratories, H. Lundbeck
Depression, Anxiety disorders
Gleevec, Glivec
Imatinib
Non amorphous
2,554
18%
Novartis
Leukemia
Ambien, Stilnox
Zolpidem
Non amorphous
2,545
33%
Sanofi-Aventis
Insomnia
Aricept
Donepezil
Non amorphous
2,519
24%
Eisai, Pfizer
Alzheimer’s disease
Epogen
Erythropoietin
Amorphous
2,511
2%
Amgen
Anemia
Zyrtec, Cirrus
Cetirizine
Non amorphous
2,377
9%
Pfizer, UCB, Daiichi Sankyo
Allergic rhinitis
Avapro, Aprovel, Avalide
Irbesartan
Non amorphous
2,372
13%
Sanofi-Aventis, Bristol-Myers Squibb
Hypertension
Avastin
Bevacizumab
Amorphous
2,364
78%
Roche, Genentech
Colorectal cancer
Taxotere
Docetaxel
Amorphous
2,201
9%
Sanofi-Aventis
Cancer
Eloxatin, Eloxatine
Oxaliplatin
Amorphous
2,127
8%
Sanofi-Aventis
Colorectal cancer
Zoloft
Sertraline
Non amorphous
2,110
-35%
Pfizer
Depression, Anxiety disorders
Tamiflu
Oseltamivir
Non amorphous
2,096
69%
Roche, Chugai Pharmaceutical
Influenza
Lantus
Insulin analog
Amorphous
2,093
37%
Sanofi-Aventis
Type 2 diabetes and type 1 diabetes
Crestor
Rosuvastatin
Rosuvastatin calcium is a white amorphous powder
2,049
61%
AstraZeneca, Shionogi
Cholesterol
Humira
Adalimumab
Amorphous
2,044
46%
Abbott Laboratories
Rheumatoid arthritis
Celebrex
Celecoxib
Non amorphous
2,039
18%
Pfizer
Osteoarthritis and rheumatoid arthritis
Topamax
Topiramate
Non amorphous
2,027
21%
Johnson & Johnson
Seizures
Prevnar
vaccine
Amorphous
1,961
30%
Wyeth
Pneumococcal disease
Vytorin
Ezetimibe + Simvastatin
Non amorphous
1,955
90%
Merck & Co., Schering-Plough
Cholesterol
Zetia
Ezetimibe
Non amorphous
1,929
38%
Merck & Co., Schering-Plough
Cholesterol
Wellbutrin
Bupropion
Non amorphous
1,926
26%
GlaxoSmithKline, Biovail
Depression, Seasonal affective disorder (SAD)
Abilify
Aripiprazole
Crystalline
1,900
1%
Otsuka Pharmaceutical, Bristol-Myers Squibb
Schizophrenia
Lamictal
Lamotrigine
Crystalline
1,843
19%
GlaxoSmithKline
Seizures
Toprol, Seloken
Metoprolol
Crystalline
1,795
3%
AstraZeneca
Hypertension
NeoRecormon, Epogin
Erythropoietin
Amorphous
1,777
-1%
Roche, Chugai Pharmaceutical
Anemia
Atacand, Blopress
Candesartan
Cristalline
1,768
8%
Takeda Pharmaceutical, AstraZeneca
Hypertension
Spiriva
Tiotropium
Cristalline
1,735
45%
Boehringer Ingelheim
Chronic obstructive pulmonary disease
Avonex
Interferon beta-1a
Amorphous
1,707
11%
Biogen Idec
Multiple sclerosis
Viagra
Sildenafil
Crystalline
1,657
1%
Pfizer
Erectile dysfunction
Micardis
Telmisartan
Crystalline
1,645
35%
Boehringer Ingelheim, Astellas Pharma
Hypertension
Actonel
Risedronate
Crystalline
1,619
-4%
Procter & Gamble, Sanofi-Aventis
Osteoporosis
Lupron, Leuplin
Leuprolide
Amorphous
1,579
1%
Takeda Pharmaceutical, TAP Pharmaceuticals
Prostate cancer
TriCor, Lipanthyl
Fenofibrate
Amorphous
1,567
38%
Abbott Laboratories, Solvay
Cholesterol
Zofran
Ondansetron
Non amorphous
1,567
3%
GlaxoSmithKline
Nausea and vomiting
Valtrex
Valaciclovir
Non amorphous
1,563
24%
GlaxoSmithKline
Herpes
Levaquin, Floxin
Levofloxacin
Non amorphous
1,530
3%
Johnson & Johnson
Bacterial infections
Arimidex
Anastrozole
Non amorphous
1,508
28%
AstraZeneca
Breast cancer
Prograf
Tacrolimus
Non amorphous
1,499
20%
Astellas Pharma
Transplant rejection
CellCept
Mycophenolate mofetil
Non amorphous
1,470
8%
Roche, Chugai Pharmaceutical
Transplant rejection
Xalatan, Xalacom
Latanoprost
Non amorphous
1,453
6%
Pfizer
Intraocular pressure
Rebif
Interferon beta-1a
Amorphous
1,452
14%
Serono
Multiple sclerosis
Coreg
Carvedilol
Non amorphous
1,441
38%
GlaxoSmithKline
Hypertension
Gemzar
Gemcitabine
Non amorphous
1,408
5%
Eli Lilly
Cancer
Prilosec, Losec
Omeprazole
Non amorphous
1,371
-17%
AstraZeneca
Gastrointestinal disorders
Benicar, Olmetec
Olmesartan
Non amorphous
1,370
73%
Daiichi Sankyo, Forest Laboratories
Hypertension
Lotrel
Amlodipine + Benazepril
Non amorphous
1,352
26%
Novartis
Hypertension
Cymbalta
Duloxetine
Non amorphous
1,316
94%
Eli Lilly
Depression, Anxiety disorders
Imitrex, Imigran
Sumatriptan
Crystalline
1,315
4%
GlaxoSmithKline
Migraine
Depakote
Valproate semisodium
Crystalline
1,308
19%
Abbott Laboratories
Seizures
Humalog
Insulin analog
Crystalline
1,300
8%
Eli Lilly
Diabetes
Duragesic
Fentanyl
Crystalline
1,295
-18%
Johnson & Johnson
Pain
Pulmicort
Budesonide
Crystalline
1,292
11%
AstraZeneca
Asthma
Zometa
Zoledronate
Crystalline
1,283
5%
Novartis
Hypercalcemia
Betaseron, Betaferon
Interferon beta-1b
Amorphous
1,245
14%
Schering AG
Multiple sclerosis
Delix, Tritace
Ramipril
Crystalline
1,227
-3%
Sanofi-Aventis
Hypertension
Flovent, Flixotide
Fluticasone
Crystalline
1,219
5%
GlaxoSmithKline
Asthma
Neupogen
Filgrastim
Amorphous
1,213
0%
Amgen
Neutropenia
Casodex
Bicalutamide
Crystalline
1,206
7%
AstraZeneca
Prostate cancer
Pravachol
Pravastatin
Crystalline
1,197
-47%
Bristol-Myers Squibb
Cholesterol
Truvada
Tenofovir + Emtricitabine
Crystalline
1,194
110%
Gilead Sciences
HIV infection
Symbicort
Budesonide + Formoterol
Crystalline
1,184
18%
AstraZeneca
Asthma
Pegasys
Pegylated interferon alfa-2a
Amorphous
1,171
5%
Roche, Chugai Pharmaceutical
Hepatitis C
Evista
Raloxifene
Non-amorphous
1,159
4%
Eli Lilly, Chugai Pharmaceutical
Osteoporosis
Flomax
Tamsulosin
Crystalline
1,158
28%
Boehringer Ingelheim
Benign prostatic hypertrophy
Lyrica
Pregabalin
Crystalline
1,156
297%
Pfizer
Neuropathic pain
Paxil, Seroxat
Paroxetine
Crystalline
1,147
3%
GlaxoSmithKline
Depression, Anxiety disorders
Kaletra
Lopinavir
Crystalline
1,135
13%
Abbott Laboratories
HIV infection
Detrol
Tolterodine
Crystalline
1,100
11%
Pfizer
Overactive bladder
Harnal
Tamsulosin
Crystalline
1,085
-8%
Astellas Pharma
Benign prostatic hypertrophy
Erbitux
Cetuximab
Amorphous
1,075
56%
Bristol-Myers Squibb, Merck KGaA
Colorectal cancer
Synagis
Palivizumab
Amorphous
1,065
-9%
MedImmune
Respiratory syncytial virus
Augmentin
Co-amoxiclav
Crystalline
1,055
-13%
GlaxoSmithKline
Bacterial infections
Premarin, Prempro, Premphase
Estrogen
Crystalline
1,051
16%
Wyeth
Menopausal symptoms
Ortho contraceptives
Estrogen + Progesterone
Crystalline
1,016
-11%
Johnson & Johnson
Contraception
Zoladex
Goserelin
Amorphous
1,008
0%
AstraZeneca
Prostate cancer
Cerezyme
Imiglucerase
Amorphous
1,007
8%
Genzyme
Gaucher disease
Cravit
Levofloxacin
Crystalline
1,002
2%
Daiichi Sankyo, Santen Pharmaceutical
Bacterial infections
Yasmin
Drospirenone
Crystalline
998
36%
Schering AG
Prevention of pregnancy
Kogenate
Recombinant factor VIII
Amorphous
989
19%
Bayer
Hemophilia
Botox
Botulin toxin
Amorphous
982
18%
Allergan
Cervical dystonia
Lamisil
Terbinafine
Crystalline
978
-14%
Novartis
Fungal infections
Combivir
Lamivudine + Zidovudine
Crystalline
977
-8%
GlaxoSmithKline
HIV infection
Zosyn, Tazocin
Piperacillin
Crystalline
972
9%
Wyeth
Bacterial infections
Cialis
Tadalafil
Crystalline
971
30%
Lilly, Lilly Icos
Erectile dysfunction
Keppra
Levetiracetam
956
36%
UCB
Seizures
NovoSeven
Factor VII
Amorphous
948
11%
Novo Nordisk
Bleeding due to hemophilia
Infanrix, Pediarix
vaccine
Amorphous
945
21%
GlaxoSmithKline
Diphtheria, tetanus, and pertussis
Nasonex
Mometasone
Non-amorphous
944
28%
Schering-Plough
Allergic rhinitis
Reyataz
Atazanavir
Non-amorphous
931
34%
Bristol-Myers Squibb
HIV infection
Concerta
Methylphenidate
Non-amorphous
930
20%
Johnson & Johnson
Attention-deficit hyperactivity disorder
Humulin
Recombinant human insulin
Amorphous
925
-8%
Eli Lilly
Diabetes
Neoral, Sandimmun
Ciclosporin
Amorphous
918
-4%
Novartis
Transplant rejection
Sandostatin
Somatostatin
Amorphous
915
2%
Novartis
Acromegaly
Camptosar
Irinotecan
Amorphous
903
-1%
Pfizer
Colorectal cancer
Engerix-B, Havrix, Twinrix
vaccine
Amorphous
886
10%
GlaxoSmithKline
Hepatitis
Allegra, Telfast
Fexofenadine
Non-amorphous
864
-49%
Sanofi-Aventis
Allergic rhinitis
Adderall
Amphetamine
Non-amorphous
864
18%
Shire Pharmaceuticals
Attention-deficit hyperactivity disorder
Combivent
Ipratropium + Salbutamol
Non-amorphous
843
20%
Boehringer Ingelheim
Chronic obstructive pulmonary disease
Peg-Intron
Pegylated interferon alfa-2b
Amorphous
837
11%
Schering-Plough
Hepatitis C
Adalat
Nifedipine
Non-amorphous
825
0%
Bayer
Hypertension
Avelox, Avalox
Moxifloxacin
Non-amorphous
822
17%
Bayer, Schering-Plough, Shionogi
Bacterial infections
Mobic
Meloxicam
Non-amorphous
818
-66%
Boehringer Ingelheim, Daiichi Sankyo
Osteoarthritis and rheumatoid arthritis
Biaxin
Clarithromycin
Non-amorphous
816
-23%
Abbott Laboratories
Bacterial infections
Mevalotin
Pravastatin
Non-amorphous
799
-35%
Daiichi Sankyo
Cholesterol
Ultane, Sevorane
Sevoflurane
Amorphous
799
-9%
Abbott Laboratories
Anesthesia
Genotropin
Somatropin
Amorphous
795
-2%
Pfizer
Growth failure
Sustiva
Efavirenz
Crystalline
791
16%
Bristol-Myers Squibb
HIV infection
Zyvox
Linezolid
Crystalline
782
27%
Pfizer
Bacterial infections
Xeloda
Capecitabine
Crystalline
775
22%
Roche, Chugai Pharmaceutical
Cancer
Geodon, Zeldox
Ziprasidone
Crystalline
758
29%
Pfizer
Schizophrenia
Cipro, Ciprobay
Ciprofloxacin
Crystalline
755
-6%
Bayer, Schering-Plough
Bacterial infections
Provigil
Modafinil
Crystalline
735
43%
Cephalon
Sleepiness
Lescol
Fluvastatin
Crystalline
725
-5%
Novartis
Cholesterol
Clarinex, Aerius
Desloratadine
Crystalline
722
12%
Schering-Plough
Allergic rhinitis
Femara
Letrozole
Crystalline
722
35%
Novartis, Chugai Pharmaceutical
Breast cancer
Trileptal
Oxcarbazepine
Crystalline
721
17%
Novartis
Seizures
Tracleer
Bosentan
717
42%
Actelion
Pulmonary arterial hypertension
Primaxin
Imipenem + Cilastatin
Amorphous
705
-5%
Merck & Co.
Bacterial infections
Temodar
Temozolomide
Crystalline
703
20%
Schering-Plough
Anaplastic astrocytoma
Trusopt, Cosopt
Dorzolamide
Crystalline
697
13%
Merck & Co.
Intraocular pressure
Voltaren
Diclofenac
Crystalline
690
0%
Novartis
Osteoarthritis and rheumatoid arthritis
Viread
Tenofovir
Crystalline
689
-12%
Gilead Sciences
HIV infection
Sifrol
Pramipexole
Crystalline
673
23%
Boehringer Ingelheim
Parkinson’s disease
Namenda
Memantine
Crystalline
660
30%
Forest Laboratories
Alzheimer disease
Altace
Ramipril
Crystalline
653
18%
King Pharmaceuticals
Cardiovascular events
Byetta
Exenatide
Amorphous
649
464%
Amylin Pharmaceuticals, Eli Lilly
Type 2 diabetes
Tarceva
Erlotinib
Crystalline
649
110%
Roche, Genentech
Non-small cell lung cancer
Zithromax, Zmax
Azithromycin
Crystalline
638
-68%
Pfizer
Bacterial infections
Omnicef
Cefdinir
Amorphous
637
29%
Abbott Laboratories
Bacterial infections
Proscar
Finasteride
Crystalline
619
-16%
Merck & Co.
Benign prostatic hypertrophy
Alimta
Pemetrexed
Amorphous
612
32%
Eli Lilly
Non-small cell lung cancer
Merrem
Meropenem
604
20%
AstraZeneca
Bacterial infections
Forteo
Teriparatide
Amorphous
594
53%
Eli Lilly
Osteoporosis
Strattera
Atomoxetine
Crystalline
579
5%
Eli Lilly
Attention-deficit hyperactivity disorder
Actiq
Fentanyl
Crystalline
578
40%
Cephalon
Cancer pain
Flonase, Flixonase
Fluticasone
Crystalline
575
-52%
GlaxoSmithKline
Allergic rhinitis
Amaryl
Glimepiride
Crystalline
567
-33%
Sanofi-Aventis
Type 2 diabetes
Lidoderm
Lidocaine
Amorphous
567
35%
Endo Pharmaceuticals
Pain
Lunesta
Eszopiclone
Non amorphous
567
72%
Sepracor
Insomnia
Boniva, Bonviva
Ibandronate
Non amorphous
565
454%
Roche, GlaxoSmithKline
Osteoporosis
Taxol
Paclitaxel
Amorphous
563
-25%
Bristol-Myers Squibb
Cancer
Zelnorm, Zelmac
Tegaserod
Non amorphous
561
34%
Novartis
Irritable bowel syndrome
Renagel
Sevelamer
Non amorphous
559
23%
Genzyme, Roche, Chugai Pharmaceutical
Hyperphosphatemia
Norditropin
Human growth hormone
Amorphous
557
19%
Novo Nordisk
Growth hormone deficiency
Xopenex
Levalbuterol
Non amorphous
555
29%
Sepracor
Bronchospasm
Xenical
Orlistat
Non amorphous
553
9%
Roche
Obesity
Vasotec, Vaseretic
Enalapril
Non amorphous
547
-12%
Merck & Co.
Hypertension
Serevent
Salmeterol
Non amorphous
538
-10%
GlaxoSmithKline
Asthma
Cardura
Doxazosin
Non amorphous
538
-8%
Pfizer
Hypertension
Synthroid
Levothyroxine
Non amorphous
534
-4%
Abbott Laboratories
Hypothyroidism
Gonal-f
Follitropin alfa
Amorphous
533
-3%
Serono
Infertility
Gaster
Famotidine
532
-10%
Astellas Pharma
Gastrointestinal disorders
Cancidas
Caspofungin
Amorphous
530
-7%
Merck & Co.
Fungal infections
Exelon
Rivastigmine
Non amorphous
525
12%
Novartis
Alzheimer’s disease
Vfend
Voriconazole
Non amorphous
515
30%
Pfizer
Fungal infections
Amlodin
Amlodipine
Non amorphous
506
4%
Dainippon Sumitomo
Hypertension, angina pectoris
Niaspan
Niacin
Non amorphous
498
13%
Kos Pharmaceuticals
Cholesterol
Neurontin
Gabapentin
Non amorphous
496
-22%
Pfizer
Seizures
Trizivir
Abacavir + Lamivudine + Zidovudine
Non amorphous
496
-10%
GlaxoSmithKline
HIV infection
Requip
Ropinirole
Non amorphous
496
74%
GlaxoSmithKline
Parkinson disease
Follistim, Puregon
Follitropin beta
Amorphous
482
8%
Akzo Nobel
Infertility
Basen
Voglibose
Non amorphous
476
-13%
Takeda Pharmaceutical
Hyperglycemia
Levitra
Vardenafil
Non amorphous
474
19%
Bayer, GlaxoSmithKline
Erectile dysfunction
Glucophage
Metformin
Non amorphous
459
-16%
Merck KGaA, Bristol-Myers Squibb
Type 2 diabetes
Concor
Bisoprolol
Non amorphous
455
4%
Merck KGaA
Hypertension
Epzicom, Kixeva
Abacavir + Lamivudine
Non amorphous
446
107%
GlaxoSmithKline
HIV infection
Xatral
Alfuzosin
Crystalline
443
8%
Sanofi-Aventis
Benign prostatic hypertrophy
Diflucan
Fluconazole
Crystalline
435
-13%
Pfizer
Fungal infections
Thalomid
Thalidomide
Crystalline
433
12%
Celgene
Erythema nodosum leprosum
Zantac
Ranitidine
Crystalline
429
-18%
GlaxoSmithKline
Gastrointestinal disorders
Xolair
Omalizumab
Amorphous
429
32%
Roche, Genentech
Asthma
Claritin
Loratadine
Crystalline
418
-5%
Schering-Plough, Shionogi & Co.
Allergic rhinitis