The document presents a research project on preparing and evaluating co-crystals of atorvastatin calcium with saccharin and urea. The objectives are to prepare the co-crystals using solvent drop grinding and solvent evaporation methods, characterize them using various techniques, and evaluate their solubility. The document outlines the materials, methods, results and discussion sections of the project including pre-formulation studies of atorvastatin calcium and the co-formers, characterization of the prepared co-crystals using FTIR, DSC and solubility testing, and evaluation of drug-excipient compatibility. The project aims to develop co-crystal formulations to improve the solubility and dissolution rate of the poorly soluble at

1. Presented By :
Rupsa S. Ghosh
M.Pharm Semester-IV
Guided by:
Prof. S. B. Bumrela
HOD, Pharmaceutics
Sinhgad Institute of Pharmaceutical Sciences, Lonavala (Pune)
Department of Pharmaceutics

2. 13 March 20152
₪ Introduction
₪ Literature Review
₪ Aims and Objectives
₪ Plan of work
₪ Materials and Methods
₪ Drug Profile
₪ Result and Discussion
₪ Summary and Conclusion
₪ References
CONTENTS

3. INTRODUCTION
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4.  Aqueous solubility is one of the key determinants in development of new
chemical entities as successful drugs.
 Formulation of poorly soluble compounds face typical problems viz a too low
oral bioavailability and erratic absorption due to their very low saturation
solubility and dissolution rate.
 The conventional methods used for improvement of solubility and dissolution
rate fails to increase the bioavailability.
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5. CO-CRYSTALS
 Co-crystal is a crystalline structure consisting of two or more components that
form a unique structure having specific properties. They are also known as
“solid crystals , multi-molecular complexes, molecular compounds, organic
molecular compounds, addition compounds, and solid state complexes”.
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6.  A pharmaceutical co-crystal is a single crystalline solid that incorporates two
neutral molecules, one being an active pharmaceutical ingredient (API) and the
other a co-crystal former.
 The components in a co-crystal exist in a definite stoichiometric ratio
(1:1;1:2;1:1.5), and assemble via non-covalent interactions such as hydrogen
bonds, ionic bonds, π-π or Vander Waals interactions rather than by ion
pairing.
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7. CO-FORMERS
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 Co-crystal former may be an excipient or another drug.
 It should have at least one functional group from amine, amide, aldehyde,
ketone, thio ketone, ether, pyridine, imidazole, indole, pyrrolidine, carboxyl,
carbonyl, phenol, sulfone, sulfonyl, mercapto and methyl thio.
 Examples: Mallic Acid, Nicotinamide, Benzoic Acid.
Saccharin Urea

8. DRUG SELECTION CRITERIA
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The ability of an API to form co-crystal depends on
 Type of co-former
 API: co-former ratio
 Solvent
 Temperature
 Pressure
 Crystallization technique

9. 13 March 20159
Advantages of Co-crystals
All types of molecules can form co-crystals
No
by products formed
An opportunity to address
Intellectual Property (IR)
issues
High
yield
techniques

10. LITRETURE REVIEW
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11. 13 March 2015
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Sr.
No.
Title Detail Of Work How Useful Ref.
No.
1 Performance
comparison of a
Co-Crystal of
Carbamazepine
with marketed
product
Physical and chemical stability of the co-
crystal is similar to the pure drug in the
marketed product (Tegretol) & oral BA in
dogs shows the co-crystal to be a viable
alternative to the anhydrous polymorph in
formulated solid oral products.
Evaluation parameters
of resultant co-
crystals. 2
2 Co-Crystals of
Efavirenz with
selected Co-
formers:
preparation and
characterization
Co-crystals were prepared using solvent drop
grinding and solvo-thermal method.
Equilibrium solubility profile of EFA-Oxalic
acid dihydrate (1:1) & EFA-Citric acid
monohydrate (1:1) shows an enhancement of
1.8 &2.7 folds of solubility of Efavirenz as
compared to commercial sample.
Method of preparation,
determination of
stoichiometric ratio of
co-formers.
3

12. 13 March 201512
3 Improving the
Solubility of
Agomelatine via
Co-crystals
Four co-crystals of Agomelatine with urea
Glycolic acid, Isonicotinamide , & Methyl4-
hydroxybenzoate in 1:1 stoichiometry were
synthesized via six kinds of synthons. The
solubility of Agomelatine is much improved in
PB pH 6.8& are approx.2.2, 2.9, 4.7, &3.5
times greater than that of Agomelatine Form II,
& 1.6, 2.1, 3.4&2.5 times than that of Form I.
Selection of
co-formers.
6
4 Characterization
of Prulifloxacin-
Salicylic Acid
Complex by
IR,DSC And
PXRD
Co-crystals of Prulifloxacin-Salicylic acid were
prepared in different molar conc. by kneading
method using mortar and pestle for 30mins
&characterized using IR,DSC, PXRD. The
resultant co-crystals showed improved
solubility and in turn dissolution rate than the
pure drug.
Time of
grinding,
solubility
and
dissolution
studies
7
Sr.
No.
Title Detail Of Work How Useful Ref.
No.

13. 13 March 2015
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AIMS AND OBJECTIVES

14. 13 March 201514
 To investigate different methods of preparation for co-crystals.
 To prepare co-crystals by solvent drop grinding and solvent evaporation
methods.
 To evaluate the physicochemical properties of prepared co-crystals.
a) Particle morphology
b) Crystalline state evaluation
- Powder X-ray Diffraction (PXRD)
- Differential Scanning Calorimetry (DSC)
c) Solubility determination of the co-crystals.
d) Formulation and optimization of co-crystals into tablet dosage form.
e) In- vitro drug dissolution study and comparison with marketed product.
f) Stability study of the optimized formulation.

15. PLAN OF WORK
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16. 13 March 201516
1.Selection of poorly soluble drugs.
2.Selection of co-crystal formers.
3.Methods of preparation: Different techniques for the preparation of co-crystals
are present. However, in the present work these following methods are used
a) Solvent drop grinding technique
b) Solvent evaporation technique
4.Physiochemical characterization of:
 Drugs and co-crystal formers.
 Prepared co-crystals.
 In- vitro dissolution studies of prepared co-crystals.
 Formulation of co-crystals into tablets.

17. 13 March 201517
5. Drug-Excipient compatibility study by FT-IR.
6. Evaluation studies of the tablet formulations .
7. Comparison of in-vitro dissolution of co-crystal formulations with marketed
products of the same drugs.
8. Optimization of the tablet formulation using 22 full factorial designs and
statistical analysis of the data.
9. Stability study of the optimized formulation as per ICH guidelines.

18. MATERIALS AND METHODS
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19. List of chemicals and their manufacturers
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Sr. No. Materials Manufacturers
1. Atorvastatin Calcium Dr. Reddy’s Lab, Hyderabad
2. Saccharine Insoluble
Shree Vardayini Chemical Industries Pvt.
Ltd., Gujarat
3. Urea
DNS Fine Chemicals and Laboratories (P)
Ltd, Mumbai
4. Croscarmellose sodium A.B. Enterprises, Mumbai
5. Microcrystalline Cellulose A.B. Enterprises, Mumbai
6. Hydroxypropyl Cellulose A.B. Enterprises, Mumbai
7. Lactose Monohydrate Shreenath Chemicals, Mumbai
8. Calcium Carbonate Oasis Fine Chemicals, Gujarat
9. Magnesium Stearate Shreenath Chemicals, Mumbai

20. DRUG PROFILE
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21. 13 March 2015
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STRUCTURE
CAS NO. 134523-00-5
IUPAC NAME (βR,8R)-2-(4-
fluorophenyl)-α,δ-dihydroxy-5-(1-
methylethyl)-3-phenyl-4-
[(phenylamino)carbonyl]-1H-pyrrole-1-
heptanoic acid trihydrate.
MOLECULAR FORMULA C66H68CaF2N4O10
MOLECULAR WEIGHT 1155.36
MELTING POINT 176-177 ºC
DESCRIPTION A white to off-white, crystalline powder.
SOLUBILITY Highly soluble in methanol
CATEGORY HMG-CoA Reductase Inhibitors
ATORVASTATIN CALCIUM

22. RESULTS AND DISCUSSION
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23. 13 March 201523
 Pre-formulation studies of Atorvastatin Calcium
1. Melting Point - 176-178 ºC
2. Solubility
3. Determination of λmax
Sr. No. Solution Inference
1. Distilled water Very slightly soluble
2. Phosphate buffer pH 6.8 Very slightly soluble
3. Ethanol (95%) Slightly soluble
4. Methanol Freely soluble
Fig1- UV spectra of Atorvastatin Calcium in methanol

24. 13 March 201524
Sr. No. Conc.(µg) Absorbance
1 5 0.1328
2 10 0.267
3 15 0.4969
4 20 0.5033
5 25 0.6091
4. Calibration curve of Atorvastatin Calcium in Methanol
Fig2- Calibration curve of ATC in methanol

25. 13 March 201525
5. Differential Scanning Calorimetry(DSC)
6. Powder X-ray diffraction (PXRD)
Fig3-DSC curve of ATC
Fig4-PXRD curve of ATC

26. 13 March 201526
 Pre-formulation studies of co-crystals
Sr. No. Parameters Observation
1 Organoleptic properties
Colour White (ATC: SAC)
Off- white(ATC:UREA)
Odour Odorless
2 Melting point
ATC +Sac ( solvent grinding)
ATC +Sac ( solvent evaporation)
187-190ºC
192-194ºC
ATC +Urea ( solvent grinding)
ATC +Urea (( solvent evaporation)
164-168ºC
168-170ºC
3 Solubility studies
Distilled water More than pure drug
Methanol Highly soluble

27. 13 March 201527
Fig5- Microscopic Photographs
A) ATC: SAC co-crystal by SE B) ATC: SAC co-crystal by SG
C) ATC: UREA co-crystal by SE D) ATC: UREA co-crystal by SG

28. 13 March 201528
Fig6- FTIR spectra of pure Atorvastatin Calcium
Peak Inference
NH =3500-3100cm-1 Stretching
OH =3650-3200cm-1 Stretching
C=O =1536cm-1 Amide
 Fourier Transform Infrared Spectroscopy (FTIR)

29. 13 March 201529
A Pure Urea
B Co-crystal (SE)
C Co-crystal (SG)
A)
B) C)
Fig 7- FTIR spectra of

30. 13 March 201530
Sr. No. IR Spectrum Peak (cm-1) Groups Inference
1. Atorvastatin
Calcium
3510.77 N-H Stretching
--1459.85 N-H Bending
1676.8 C=O Amide
3580.2 O-H Stretching
2.
Urea 1691.27 C=O Ketone
--3505.95 N-H Stretching
3600.3 O-H Free
3.
ATC: UREA co-
crystal (SE)
3510.77 N-H Stretching Confirms
formation of inter-
molecular H- bond
1459.85 N-H Bending
3442.31 O-H Bonded
4.
ATC: UREA co-
crystal (SG)
3510.77 N-H Stretching Confirms
formation of inter-
molecular H- bond
1459.85 N-H Bending
3444.24 O-H Bonded
FT-IR interpretation of Atorvastatin Calcium: UREA co-crystals

31. 13 March 201531
A Pure saccharine
B Co-crystal(SG)
C Co-crystal(SE)
Fig8- FTIR spectra of
A)
B) C)

32. 13 March 201532
Sr. No. IR Spectrum Peak (cm-1) Groups Inference
1. Atorvastatin
Calcium
3510.77 N-H Stretching
--1580.38 N-H Bending
1676.8 C=O Amide
3580.2 O-H Stretching
2.
Saccharin 1723.09 C=O Ketone
--3613.95 O-H Stretching
1055 O=S=O
Sulfones
1337.39 C-N
3.
ATC: SAC
co-crystal (SE)
1728.44 C=O Ketone Confirms
formation of inter-
molecular H- bond
3666.36 O-H Stretching
4. ATC: SAC
co-crystal (SG)
1728.36 C=O Ketone Confirms
formation of inter-
molecular H- bond
3706.06 O-H Stretching
FT-IR interpretation of Atorvastatin Calcium: Saccharin co-crystals

33. 13 March 201533
 Drug- excipient compatibility
Fig 9- FT-IR spectra of
Physical mixture of ATC:
SAC co-crystal and excipients
a) ATC : SAC co-crystal +
Calcium carbonate
b) ATC: SAC co-crystal +
Croscarmellose Sodium
c) ATC: SAC co-crystal +
Microcrystalline Cellulose
d) ATC: SAC co-crystal+
Hydroxypropyl Cellulose
e) ATC: SAC co-crystal+
Lactose Monohydrate
f ) ATC: SAC co-crystal+
Magnesium stearate

34. 13 March 201534
Fig 10- FT-IR spectra of Physical
mixture of ATC: UREA co-
crystal and excipients
a) ATC: UREA co-crystal+
Calcium carbonate
b) ATC: UREA co-crystal+
Croscarmellose Sodium
c) ATC: UREA co-crystal+
Microcrystalline Cellulose
d) ATC: UREA co-crystal+
Hydroxypropyl Cellulose
e) ATC: UREA co-crystal+
Lactose Monohydrate
f) ATC: UREA co-crystal+
Magnesium stearate

35. 13 March 201535
 Characterization of co-crystals
1. . Differential Scanning Calorimetry(DSC)
Fig11- DSC curves of
a) Pure ATC
b) ATC: SAC co-crystal (SE)
c) ATC: SAC co-crystal (SG)
d) ATC: Urea co-crystal (SE)
e) ATC: Urea co-crystal (SG)

36. 13 March 201536
2. Powder X-ray diffraction (PXRD)
Fig12- Powder X-ray
diffraction patterns of ATC
and Co-crystals.

37. 13 March 201537
1 Media 900ml of PB pH 6.8
2 Time 30mins
3 Apparatus USP-II
4 Speed 75rpm
3. In-vitro dissolution of co-crystals
Fig13 - Comparative dissolution profiles of drug and ATC: SAC co-crystals

38. 13 March 201538
1 Media 900ml of PB pH 6.8
2 Time 30mins
3 Apparatus USP-II
4 Speed 75rpm
Fig14- Comparative dissolution profiles of drug and ATC: UREA co-crystals

39. 13 March 201539
 Formulation design of Atorvastatin Calcium co-crystal tablets
1. Preparation of tablet granules by wet granulation technique
Weighed quantity of Co-crystal+
half quantity of CCS+ HPC+
Lactose monohydrate all passed
through sieve 40
Granulation with distilled water &
drying at 55ºC in Hot air oven for
2hrs.
Prepared granules are shifted
through sieve30 &mixing of rest
amount of CCS for 10mins
Addition of Magnesium
sterate & mixing for 5mins
Granules ready for
compression

40. 13 March 201540
 Optimization of tablet formulation by 22 full factorial designs
 Factors used:
The amount of Croscarmellose Sodium (X1)
Hydroxypropyl Cellulose (X2)
 Levels used:
High level (+1)
Low level (-1)
 Responses measured:
Drug release (Y1)
Hardness (Y2)

41. 13 March 201541
Sr. No. Ingredients
(mg/tablet)
F1 F2 F3 F4
1. ATC: Sac co-
crystal(SE)
20 20 20 20
2. Croscarmellose
Sodium
3 6 3 6
3. Microcrystalline
Cellulose
50 50 50 50
4. Hydroxypropyl
Cellulose
4 10 10 4
5. Lactose
Monohydrate
120 111 120 111
6. Calcium
Carbonate
1 1 1 1
7. Magnesium
Stearate
2 2 2 2
Formulation design for Atorvastatin Calcium: Saccharine co-crystal
(Solvent evaporation technique) tablets

42. 13 March 201542
Sr. No. Ingredients
(mg/tablet)
F5 F6 F7 F8
1. ATC: Urea co-
crystal(SE)
20 20 20 20
2. Croscarmellose
Sodium
3 6 3 6
3. Microcrystalline
Cellulose
50 50 50 50
4. Hydroxypropyl
Cellulose
4 10 10 4
5. Lactose
Monohydrate
120 111 120 111
6. Calcium
Carbonate
1 1 1 1
7. Magnesium
Stearate
2 2 2 2
Formulation design for Atorvastatin Calcium: Urea co-crystal
(Solvent evaporation technique) co-crystal tablets

43. 13 March 201543
Sr. No. Ingredients
(mg/tablet)
F9 F10 F11 F12
1. ATC: Sac co-
crystal(SG)
20 20 20 20
2. Croscarmellose
Sodium
3 6 3 6
3. Microcrystalline
Cellulose
50 50 50 50
4. Hydroxypropyl
Cellulose
4 10 10 4
5. Lactose
Monohydrate
120 111 120 111
6. Calcium
Carbonate
1 1 1 1
7. Magnesium
Stearate
2 2 2 2
Formulation design for Atorvastatin Calcium: Saccharine co-crystal
(Solid grinding technique) co-crystal tablets

44. 13 March 201544
Sr. No. Ingredients
(mg/tablet)
F13 F14 F15 F16
1. ATC: Sac co-
crystal(SG)
20 20 20 20
2. Croscarmellose
Sodium
3 6 3 6
3. Microcrystalline
Cellulose
50 50 50 50
4. Hydroxypropyl
Cellulose
4 10 10 4
5. Lactose
Monohydrate
120 111 120 111
6. Calcium
Carbonate
1 1 1 1
7. Magnesium
Stearate
2 2 2 2
Formulation design for Atorvastatin Calcium: Urea co-crystal
(Solid grinding technique) co-crystal tablets

45. 13 March 201545
 Contour Plots
Fig-15 -Contour Plot of factorial variables on
Hardness. The shaded region indicates the
range of response variable Hardness (Y2)
Fig16 - Contour Plot of factorial variables on
Drug Release. The shaded region indicates the
range of response variable, Drug Release (Y1)

46. 13 March 201546
 Response-surface analysis
Fig17- Response surface plot of factorial
variables (CCS & HPC) on Hardness. The
shaded region indicates the range of response
variable, Hardness (Y2)
Fig18 - Response surface plot of factorial
variables (CCS & HPC) on Drug Release. The
shaded region indicates the range of response
variable, Drug Release (Y1)

47. 13 March 201547
 Statistical Analysis using ANOVA
Response 2 Hardness
ANOVA for selected factorial model
Analysis of variance table [Partial sum of squares - Type
III]
Sum of
squares
d
f
Mea
n
Squa
re
F
Valu
e
p-
valu
e
Pro
b >
FSource
Model 2.002225 1
2.00
2225
59.5
4572
0.01
64
signif
icant
B-Hydroxy
Propryl
Cellulose 2.002225 1
2.00
2225
59.5
4572
0.01
64
Residual 0.06725 2
0.03
3625
Cor Total 2.069475 3
Response 1 Drug Release
ANOVA for selected factorial model
Analysis of variance table [Partial sum of squares - Type
III]
Sum
of
Squa
res df
Mea
n
Squa
re
F
Valu
e
p-
valu
e
Pro
b >
FSource
Model
45.0
0085 2
22.5
0043
241.
875
0.04
54
signi
fican
t
B-Hydroxy
Propryl
Cellulose
38.8
7523 1
38.8
7523
417.
9008
0.03
11
AB
6.12
5625 1
6.12
5625
65.8
4923
0.07
81
Residual
0.09
3025 1
0.09
3025
Cor Total
45.0
9388 3

48. 13 March 201548
 Evaluation of precompression parameters
Sr. No. Parameters F1 F2 F3 F4
1 Bulk
density(g/ml)
0.465 0.482 0.477 0.496
2 Tapped
density(g/ml)
0.570 0.595 0.582 0.611
3 Hausner’s ratio 1.23 1.23 1.22 1.23
4 Compressibility
index
19.29 18.99 18.04 18.82
5 Angle of
repose(º)
28.81 31.46 29.24 30.52
Pre compression parameters of ATC: SAC co-crystal (SE) granules

49. 13 March 201549
Sr. No. Parameters F5 F6 F7 F8
1 Bulk
density(g/ml)
0.505 0.512 0.515 0.523
2 Tapped
density(g/ml)
0.610 0.630 0.612 0.621
3 Hausner’s ratio 1.22 1.11 1.18 1.18
4 Compressibility
index
18.03 16.33 15.84 15.78
5 Angle of
repose(º)
30.96 33.02 31.38 29.68
Pre compression parameters of ATC: UREA co-crystal (SE) granules

50. 13 March 201550
Sr. No. Parameters F9 F10 F11 F12
1 Bulk
density(g/ml)
0.536 0.559 0.521 0.547
2 Tapped
density(g/ml)
0.620 0.644 0.620 0.632
3 Hausner’s ratio 1.16 1.09 1.19 1.16
4 Compressibility
index
14.51 13.19 16.12 14.28
5 Angle of
repose(º)
33.42 34.75 34.24 33.60
Pre compression parameters of ATC: SAC co-crystal (SG) granules

51. 13 March 201551
Sr. No. Parameters F13 F14 F15 F16
1 Bulk
density(g/ml)
0.544 0.568 0.564 0.532
2 Tapped
density(g/ml)
0.645 0.658 0.661 0.629
3 Hausner’s ratio 1.18 1.15 1.17 1.18
4 Compressibility
index
15.85 13.67 14.67 15.42
5 Angle of
repose(º)
31.42 32.33 33.56 32.33
Pre compression parameters of ATC: UREA co-crystal (SG) granules

52. 13 March 201552
 Evaluation of post compression parameters
Sr. No. Batch Hardness
(kg/cm2)
Friability
(%)
Thickness
(mm)
Weight
variation(mg)
Disintegration
time (min.)
Drug content
(%)
1 F1 5.0 0.481 2.95±0.01 200.25±1.90 15.30 99.1
2 F2 5.50 0.466 3.00±0.02 199.50±1.56 15.50 100.2
3 F3 5.50 0.524 2.70±0.04 201.15±1.92 15.60 98.4
4 F4 4.50 0.582 2.98±0.01 200.50±1.62 15.00 100.1
5 F5 5.0 0.524 2.99±0.01 199.25±1.36 18.30 99.5
6 F6 5.50 0.550 2.95±0.04 198.50±1.58 18.00 99.4
7 F7 5.30 0.542 2.98±0.01 202±1.92 17.30 100.2
8 F8 5.20 0.426 3.00±0.02 200.25±1.90 17.00 99.1
9 F9 5.30 0.424 2.96±0.03 200±1.72 17.00 98.5
10 F10 5.0 0.422 3.00±0.01 201.75±1.85 18.30 98.8
11 F11 5.30 0.426 2.97±0.05 199.90±1.80 16.60 99.2
12 F12 5.0 0.532 3.00±0.02 201.25±1.88 17.00 98.1
13 F13 5.5 0.563 2.95±0.06 198.25±1.70 18.30 98.2
14 F14 5.20 0.542 2.98±0.02 200.50±1.80 16.00 99.1
15 F15 5.5 0.550 3.00±0.01 198.90±1.55 16.30 98.5
16 F16 5.5 0.528 2.96±0.04 199.50±1.58 16.60 98.8

53. 13 March 201553
 In-vitro drug dissolution studies for ATC co-crystal tablets.
Fig19-Comparative in-vitro drug
dissolution profiles for ATC: UREA co-
crystal tablets (SE)
Fig20- Comparative in-vitro drug
dissolution profiles for ATC: SAC
co-crystal tablets (SE)

54. 13 March 201554
Fig22-Comparative in-vitro drug
dissolution profiles for ATC: UREA
co-crystal tablets (SG)
Fig21- Comparative in-vitro drug
dissolution profiles for ATC: SAC co-
crystal tablets (SG)

55. 13 March 201555
 Comparison with Marketed product
Fig23- Comparative in-vitro drug dissolution profiles for Optimized
formulation (F4) and Marketed product

56. 13 March 201556
 Stability study of optimized formulation
Condition Physical
Appearance
Dissolution
(In 30 min)
Assay (%)
Initial
40°C/75% RH
(HDPE)
White 98.73 100.1
1 month
40°C/75% RH
(HDPE)
White 97.2 100.3

57. CONCLUSION
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57

58. 13 March 2015
58
 Four co-crystals of ATC were prepared using two different co-crystal formers,
saccharin and urea and two methods of preparation, solvent evaporation and
solid grinding.
 The co-crystals showed improved solubility and in turn higher dissolution rate
than the pure drug indicating co-crystal approach as a novel and valuable means
to alter the physical characteristics of an API without chemical modification.
 Sixteen formulations of ATC co-crystal tablets were successfully formulated by
wet granulation technique.

59. 13 March 201559
 The prepared tablets were evaluated for both pre and post compression
parameters .
 Based on the results, ATC: SAC co-crystal and solvent evaporation method
was found to be more suitable than ATC: UREA co-crystal and solid grinding
method.
 Amongst all 16 formulations of Atorvastatin Calcium co-crystal tablets,
formulation F4 was found to be superior.
 The in-vitro drug release of optimized formulation was 98.03% in 30min with
an average hardness of 4.5kg/cm2.

60. 13 March 201560
• The optimized formulation (F4) was also compared with marketed tablets of
Atorvastatin Calcium .
• From the findings, it may be concluded that the formulated tablets of
Atorvastatin Calcium co-crystals showed improved solubility characteristics
and in-vitro drug release profile as compared to pure ATC. This in turn may be
responsible for achieving higher oral bioavailability and better therapeutic
effect.

61. REFERENCES
13 March 2015
61

62. 13 March 201562
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