. 2022 Sep 21;14(10):2003. doi: 10.3390/pharmaceutics14102003

Table 1.

Conditions of preparation of co-amorphs by ball milling method.

#	Drug 1	Drug 2 Molar-Ratio	Amorphous Stability (Storage-Conditions)	Mill Type	Volume Cell Material	Balls-Num. Material and Sample Weight	Milling Frequency	Milling Temp. (°C)	Milling Time	Ref.
1A	Mebendazole	Twenty different amino acids 1:1	Not reported	Oscillatory ball mill	25 mL Jar	2 (d = 12 mm) stainless steel balls 1000 mg	30 Hz	Not specified	1, 5, 15, 30, and 60 min	[84]
	Carvedilol
	Carbamazepine
	Simvastatin
	Indomethacin
	Furosemide
2A	Furosemide	Arginine	Dry conditions at 25 °C or 40 °C for 15 months of storage	Oscillatory ball mill	25 mL Jar	2 (d = 12 mm) stainless steel balls 750 mg	30 Hz	5 °C	180 min	[85]
	Nitrofurantoin	Arginine
	Cimetidine	Citrulline
	Mebendazole	Citrulline
3A	Sulfathiazole	Polyvinylpyrrolidone Xpvp: 0.6 and 0.7	Storage at 4 °C over a year	Planetary mill	50 cm³ ZrO₂ milling jars	3 balls (d = 20 mm) ZrO₂. 2.5 g	6.6 Hz	Room temperature	10 h (15 h total) 10 min pauses after every 20 min	[86]
3A	Sulfadimidine	Polyvinylpyrrolidone Xpvp: 0.6 and 0.7	Storage at 4 °C over a year	Planetary mill	50 cm³ ZrO₂ milling jars	3 balls (d = 20 mm) ZrO₂. 2.5 g	6.6 Hz	Room temperature	10 h (15 h total) 10 min pauses after every 20 min	[86]
4A	Naproxen	Cimetidine 1:2, 1:1, 2:1	Dry conditions at 4, 25 and 40 °C for up to 33 days or further extended to 186 days	Oscillatory ball mill	25 mL stainless steel milling jar	2 (d = 12 mm) stainless steel balls 1 g of sample per grinding cell	30 Hz	4 °C ± 2 °C	60 min	[87]
5A	γ-Indomethacin	Ranitidine hydrochloride 2:1, 1:1, 1:2	Dry conditions at 4, 25, and 40 °C up to 30 days	Oscillatory ball mill	25 mL stainless steel milling jar	2 (d = 12 mm) stainless steel balls 1 g of sample per grinding cell	30 Hz	4 °C ± 2 °C	60 min	[28]
6A	γ-Indomethacin	None	Not reported	Oscillatory ball mill	25 mL stainless steel milling jar	6 (d = 9 mm) stainless steel balls 1 g of sample per grinding cell	30 Hz	4 °C ± 2 °C	6 h	[88]
6A	α-Indomethacin	None	Not reported	Oscillatory ball mill	25 mL stainless steel milling jar		30 Hz	immersion in liquid nitrogen	6 h	[88]
7A	Tadalafil	None	Not reported	6770 SPEX freezer/mill	Stainless steel vessel	Stainless steel rod (no balls) 1 g of sample per grinding cell	15 Hz	Cryogenic temperature (liquid nitrogen)	10 min grinding, 3 min cool-down (2 h total)	[26]
7A	Tadalafil	None	Not reported	Planetary ball mill	250 mL zirconium jar	6 zirconia balls (d = 20 mm) 16 g of sample per grinding cell	6.6 Hz	Room temperature	15 min cycles, 5 min breaks (24 h total)	[26]
8A	Glibenclamide	None	Not reported	6770 SPEX freezer/mill	Stainless steel vessel	Stainless steel rod (no balls) 1 g	15 Hz	Cryogenic temperature (liquid nitrogen)	6 min grinding, 3 min cool-down (3 h total)	[89]
9A	Trehalose dihydrate	None	Not reported	Spex SamplePrep 6870 freezer/mill	Polycarbonate vials (23.9 cm³) with steel end caps	Magnetic rod (no balls) 1 g	15 cycles per second	Cryogenic temperature (liquid nitrogen)	2 min milling, 1 min of cool-down (30 min total)	[90]
10A	Atenolol	Hydrochlorothiazide 1:1, 1:2, and 2:1	Stored in desiccators at 4 °C and 25 °C for 30 days	6770 SPEX freezer/mill	Airtight tube	1 g	10 Hz	Cryogenic temperature (liquid nitrogen)	2 min milling, 2 min cool down (48 min total)	[91]
11A	Furosemide	Tryptophan 1:1	Not reported	Oscillatory ball mill	25 mL jars	2 stainless steel balls (d = 12 mm) 500 mg	30 Hz	6 °C	90 min	[92]
11A	Indomethacin	Arginine	Not reported	Oscillatory ball mill	25 mL jars	2 stainless steel balls (d = 12 mm) 500 mg	30 Hz	6 °C	90 min	[92]
12A	Dexamethasone	None	Not reported	High-energy planetary mill	43 cm³ ZrO₂ milling jars	7 ZrO₂ balls (d = 15 mm) 1.1 g	6.6 Hz	Room temperature	15 min milling, 5 min cool down (12 h total)	[27]
13A	α-Lactose	None	Not reported	Planetary ball mill	12 cm³ stainless steel jar	50 stainless steel balls (d = 5 mm) 1 g	6.6 Hz	30 ± 5% relative humidity and 22 ± 3 °C	20 min milling, 5 min cool down (1–20 h total)	[93]
14A	α-D-Glucose	None	Not reported	High-energy planetary mill	45 cm³ ZrO₂ milling jar	7 ZrO₂ balls (d = 1.5 cm) 1 g	5 Hz	−15 °C	20 min milling 10 min cool down (1 and 14 h total)	[68]
14A	α-D-Glucose	None	Not reported	High-energy planetary mill	45 cm³ ZrO₂ milling jar	7 ZrO₂ balls (d = 1.5 cm) 1 g	5 Hz	25 °C	20 min milling 10 min cool down (1 and 14 h total)	[68]
15A	Mebendazole	Aspartame 1:1/1:1:1	Stored in desiccators at 40 °C and 25 °C up to 4 months	Oscillatory ball mill	25 mL ball milling jars	2 stainless steel balls (d = 12 mm) 500 mg	30 Hz	5 °C (cold room)	90 min	[94]
	Tadalafil	Phenylalanine 1:1/1:1:1
	Piroxicam	Phenylalanine 1:1/1:1:1
16A	α-D-Glucose	None	Not reported	High-energy planetary mill	45 cm³ ZrO₂ milling jar	7 ZrO₂ balls (d = 1.5 cm) 1 g	5 Hz	−15 °C	20 min milling, 10 min cool down (1, 14 h total)	[95]
16A	β-Glucose	None	Not reported	High-energy planetary mill	45 cm³ ZrO₂ milling jar	7 ZrO₂ balls (d = 1.5 cm) 1 g	5 Hz	25 °C	20 min milling, 10 min cool down (1, 14 h total)	[95]
17A	Carvedilol	11 different amino acids 1:1	Stored at 25 °C under dry conditions for up to 2 years	Mixer mill MM400	25 mL stainless steel jars	2 stainless steel balls (d = 12 mm) 1000 mg	30 Hz	6 °C (cold room)	90 min	[31]
	Carbamazepine
	Furosemide
	Indomethacin
	Mebendazole
	Simvastatin
18A	Salts of indomethacin	Lysine 1:1	Stored at 25 °C, and 40 °C under dry conditions up to 36 weeks	Vibrational ball mill	25 mL milling jars	2 stainless steel balls (d = 12 mm) 1000 mg	30 Hz	6 °C (cold room)	60 min	[96]
19A	Mebendazole	Tryptophan Xdrug = 0.1, 0.3, and 0.5	Not reported	Vibrational ball mill	50 mL stainless steel jars	2 stainless steel balls (d = 12 mm)	30 Hz	Room temperature	60, 120, and 150 min	[97] unpublished data
20A	18 different drugs	NaTC natural bile acid surfactant sodium taurocholate 1:1	Stored at 22 ± 2 °C	Oscillatory ball mill	25 mL stainless steel jar	1 stainless steel ball (d = 15-mm) 1 g	25 Hz	Room temperature and −10 ± 2 °C	180 min. total time, with 10 min. break every 30 min	[37]
20A	18 different drugs	NaTC natural bile acid surfactant sodium taurocholate 1:1	Stored at 22 ± 2 °C	Oscillatory ball mill	25 mL stainless steel jar	1 stainless steel ball (d = 15-mm) 1 g	25 Hz	Room temperature and −10 ± 2 °C	120 min, with 7.5 min breaks cooled in liquid nitrogen	[37]
21A	Carbamazepine	Arginine	Not reported	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 500 mg	30 Hz	6 °C	90 min	[98]
	Indomethacin	Phenylalanine
	Indomethacin	Tryptophan
22A	(S)-Naproxen	L-arginine	Stored at 25 °C, and 40 °C under dry conditions	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 1 g	30 Hz	6 °C	60 min	[99]
23A	Griseofulvin	Aspartic Ac	Stored at 23–28 °C under dry conditions up to 12 months	High-energy planetary ball mill	Stainless steel crucible	3 stainless steel balls 2.5 g	9.3 Hz	Not specified	6 h, with 0.5 min pauses every 30 min	[100]
		Lysine
		Methionine
		Valine
		Tryptophan
24A	Naproxen	Tryptophan and proline	Stored at 40 °C under dry conditions up to 332 days	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 1 g	30 Hz	6 °C	90 min	[101]
25A	Mebendazole	None	Stored at 40 °C under dry conditions up 4 weeks or 3 months	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 500 mg	30 Hz	5 °C	90–180 min	[102]
		Dipeptide 1:1
		Aminoacid mixtures 1:1:1
26A	Oxaprozin	RameβCD 1:1	Not reported	High-energy vibrational micro mill	Not specified	Not specified	24 Hz	Not specified	30 min	[103]
26A	Oxaprozin	RameβCD-Arg. 1:1:1	Not reported	High-energy vibrational micro mill	Not specified	Not specified	24 Hz	Not specified	30 min	[103]
27A	Furosemide	Arginine 1:1	Not reported	Vibrational ball milling	25 mL stainless steel jar	2 stainless steel ball (d = 9 mm) 500 mg	25 Hz	6 °C	99 min	[104]
	γ-Indomethacin
	γ-Indomethacin + CA
28A	Indomethacin	L-tryptophan 1:1	Not reported	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 1500 mg	30 Hz	6 °C	0, 5, 15, 30, 45, 60, and 90 min. 3 or 6 h	[105]
28A	Furosemide	L-tryptophan 1:1	Not reported	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 1500 mg	30 Hz	6 °C	0, 5, 15, 30, 45, 60, and 90 min. 3 or 6 h	[105]
29A	Naproxen	Naproxen sodium 2:1, 1:1, and 1:2	Stored at 40 °C under dry conditions up to 2 weeks or 2 months	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 500 mg	30 Hz	4 °C	90 min	[106]
30A	Carvedilol	Glutamic Ac	Not reported	Vibrational ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 700 mg	30 Hz	6 °C	60 min	[107]
30A	Carvedilol	Aspartic Ac	Not reported	Vibrational ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 700 mg	30 Hz	6 °C	60 min	[107]
31A	Indomethacine	Arginine	Stored in refrigerator (≈5 °C)	Mixer mill MM400	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 500 mg	30 Hz	Not specified	60 min, with 10 min pauses; cell would be in liquid nitrogen for 2 min	[36]
		Phenylalanine
		Tryptophan
32A	Simvastatin	Lysine	Stored in desiccators at 4 °C	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 15 mm) 500 mg	30 Hz	Not specified	60 min. with 10 min. pauses cell would be in liquid nitrogen for 2 min	[108]
	Simvastatin	Serine
	Glibenclamide	Threonine
	Glibenclamide	Aspartic acid
33A	Indomethacin	Arginine	Stored at 40 °C under dry conditions	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 500 mg	30 Hz	6 °C	90 min	[98]
	Indomethacin	Tryptophan
	Carbamazepine	Tyrosine
	Carbamazepine	Phenylalanine
34A	Indomethacin	Tryptophan	-	Oscillatory mill	12 mL Stainless steel jar	2 stainless steel ball (d = 10 mm) 1.2 g	10.83 Hz	Not specified	360 min	[109]
35A	Carbamazepine	Citric acid	Stored at 40 °C under dry conditions up to 2 months	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 12 mm) 500 mg	30 Hz	4 °C	90–180 min	[110]
36A	Arginine	Glibenclamide 1:1	Stored at 4 °C, room temperature, and 40 °C up to 13 months	Oscillatory ball mill	25 mL milling chambers	2 stainless steel balls (d = 12 mm) 500 mg	30 HZ	Not specified	60 min, chambers were cooled in liquid nitrogen	[111]
	Serine
	Quercetin
37A	Glutamic ac	Mebendazole 1:1 and 1:1:1	Stored at 40 °C and 25 °C in desiccators under dry conditions up to 6 months	Oscillatory ball mill	25 mL stainless steel jar	2 stainless steel ball (d = 1.2 cm) 500 mg	30 Hz	5 °C (cold room)	30, 60, and 90 min	[112]
	L-arginine
	Glutamic Ac-Arginine
	Arginine-glutamic ac
	Glutamic-arginine
38A	Mefenamic acid	Meglumine 1:1, 1:2, and 1:4	Not reported	Planetary ball mill	Not specified	5 stainless steel balls (d = 10 mm)	4.16 Hz	Not specified	20 min	[113]
38A	Indomethacin	PVP 1:1, 1:2, and 1:4	Not reported	Planetary ball mill	Not specified	5 stainless steel balls (d = 10 mm)	4.16 Hz	Not specified	20 min	[113]
39A	L-methionine	Rutin 1:1, 1:2, 2:1	Not reported	Planetary ball mill	45 mL zirconia jar	8 YTZ balls (d = 10 mm)	10 Hz	Room temperature	12 h with a break every 10 min	[114]
	Naringin hydrate
	Quercetin dihydrate
	Hesperidin Chlorothiazide Indapamide Triamterene Nifedipine
40A	Benzamidine	Gliclazide 1:1, 1:5, or 5:1	Stored in a desiccator at 22 ± 2 °C, and 40 °C under relative humidity up to 180 days	Oscillatory ball mill	25 mL stainless steel milling jar	Stainless steel ball (d = 15 mm) 0.25 g	25 Hz	Cromilling inmersing jars in liquid nitrogen for 5 min prior to milling. 7.5 min milling	180 min, with a cool down period of 15 min after every 30 min	[38]
41A	Arginine	Quercetin 1:1, 1:2	Not reported	Not specified	25 mL stainless steel	1–3 stainless steel ball (d = 18, 15, and 12 mm)	Not specified	2 h	Not specified	[115]
	Glutamic acid
	Aspartic acid
	Tryptophan
	Glycin
42A	Candesartan cilexetil	Hydrochlorothiazide	Stored at 4 °C, 30 °C, and 40 °C under dry conditions up to 90 days	Planetary ball mill	125 mL stainless steel grinding jars	3 stainless steel grinding balls (d = 10-mm) 2 g	9.3 Hz	Room temperature	2.5 h	[116]
		Hydroxypropyl methylcellulose
		Acetate succinate (HPMCAS) type M