This document presents a study on the design and evaluation of sustained release solid dispersions of Verapamil Hydrochloride. Verapamil Hydrochloride was used as a model drug to prepare solid dispersions with different polymers like HPMC K4M and Eudragit in order to prolong its release. Various evaluation tests were performed on the solid dispersions including drug content uniformity, FT-IR, micromeritic properties, in-vitro drug release and drug release kinetics. The results showed that solid dispersions with HPMC K4M were able to sustain the drug release for up to 16 hours while those with Eudragit sustained it for up to 10-12 hours only. Thus HPMC K

1. Bengal School of Technology
A Presentation submitted on –
Design and Evaluation of Sustained Release Solid
Dispersions of Verapamil Hydrochloride
(Based on the work of S.K.Swain*
, Ch. Niranjan
Patra, J.Sruti, M.E. Bhanoji Rao)
Name- ANAL MONDAL
M.PHARM 1st Year
PHARMACEUTICS

2. INTRODUCTION
 Solid dispersions are a dispersion of one (or) more active ingredients in
an inert carrier (or) matrix in the solid state prepared by the melting
and solvent evaporation method.
 Such formulations are considered as a matrix system that helps in
prolonging the duration drug release and hence are considered suitable
for formulation as sustained release dosage forms.
 These sustained release solid dispersion system may be useful for
enhancing bioavailability and suitable for sustained release
formulations.

3. VERAPAMIL HYDROCHLORIDE
 Verapamil hydrochloride (VPH) is a Calcium channel- blocking agent used in the
treatment of angina pectoris, hypertension and cardiac arrthymia.
 It is completely absorbed from the gastrointestinal tract. Its biological half- life
is 4 to 6 hours with a usual dose of 40 to 240 mg three times a day.
 Because of the high frequency of administration and short biological half-life,
Verapamil hydrochloride was considered as an ideal drug for designing SR
formulations.

4. MATERIALS REQUIRED
 Verapamil hydrochloride
 HPMC K4M (Hydroxypropylmethylcellulose)
 Eudragit
 Methanol
 0.1 N HCl
 Potassium dihydrogen phosphate
 sodium hydroxide

5. METHODS
Preparation of sustained release solid dispersions (SDs)
 Prepared by the solvent method.
 The weighed amounts of drug and polymer (HPMCK4M, Eudragit -RSPO and
their combinations) were dispersed in a given volume of methanol.
 Stirred for 15 minutes to ensure homogenous mixing.
 The dispersions were then evaporated to dryness by storing it in a desicator
under vacuum,
 The mass was then pulverized and fractioned.
 Size fraction which passed through sieve #40 and retained on #60 i.e.
(#40/60) was selected for further studies.

6. Evaluation methods for sustained
release solid dispersions (SDs)
Drug content uniformity
 Accurately weighed amount of solid dispersions was dissolved in 0.1N HCl in 100
ml volumetric flask.
 The solution was then suitably diluted with 0.1N HCl and assayed for drug
content at an absorbance of 278 nm using UV Visible Spectrophotometer.
Drug polymer interaction studies by FT-IR spectroscopy
 FT- IR spectra for the pure drug and various physical mixtures were obtained in
FT-IR in the transmission mode with the wave number region 4,000 - 500 cm-1.
 KBr pellets were prepared by gently mixing 1 mg sample powder with 100mg
KBr.

7. Evaluation of micromeretic properties of solid dispersions and physical mixtures.
Angle of repose
 Static angle of repose were determined by the funnel method.
 Solid dispersions were taken in the funnel.
 The solid dispersions were allowed to flow through the funnel freely on to the
surface. Angle of repose was calculated using the following equation -
Tan θ = h/r
 Where ‘h’ and ‘r’ are the height and radius of the powder cone.
Bulk density
 A quantity (10 gm) of solid dispersions from each formula shaken was introduced
into a 10-mL measuring cylinder.
 After the initial volume was observed, the cylinder was allowed to fall under its
own height onto hard surface from the height of 2.5 cm at 2-second intervals.

8. In-vitro dissolution rate studies
 The dissolution study for the prepared solid dispersions were carried out using
USP XXI Dissolution Test Apparatus-1 in 900 ml of 0.1N HCl maintained at
37±0.5°C, 100 rpm.
 The samples of 5 ml were withdrawn at predetermined time interval using
pipette.
 The collected samples were suitably diluted and absorbance was measured
spectrophotometrically at 278 nm.
Drug release kinetics
 In order to establish the mechanism of release of drug, the experimental data
was fitted to different kinetic models.
 The drug release data were subjected to various mathematical kinetic models
like zero order; first order, Higuchi’s model and Korsmeyer plot.

9. DATA ANALYSIS
 To analyze the order and mechanism of the drug release the
dissolution was fitted to various equations like
 Cumulative % drug release (Vs) Time (Zero order plot).
 Cumulative % drug release (Vs) Square root of time (Higuchi’s
plot).
 Log cumulative % drug remaining (Vs) Time (First order plot).
 Log % drug release (Vs) Log Time (Korsmeyer Plot).

10. RESULTS & DISCUSSIONS
 Table 1 - In-Vitro Dissolution
kinetics of Verapamil hydrochloride
solid dispersions

 Table 2 - Tabulation for
micromeritic properties, (Mean ±
S.D)
Formulation Drug release kinetics (R2) Korsmeyer R
exponent
elease
(n)
Zero-order First-order Higuchi type
F1 0.8137 0.9812 0.9904 0.8977
F2 0.8074 0.9894 0.9937 0.8382
F3 0.8501 0.9757 0.9896 0.8272
F4 0.6148 0.9581 0.9652 0.7548
F5 0.9313 0.9393 0.9945 0.8712
F6 0.8401 0.9849 0.9982 0.7355
F7 0.8645 0.9741 0.9856 0.7488
F8 0.8439 0.9880 0.9886 0.7319
F9 0.8234 0.9833 0.9850 0.7414
Micromeritic Properties Verapamil hydrochloride Physical Mixtures Solid Dispersions
Angle of repose (in degree) 52 ± 0.12 37 ± 0.21 23 ± 0.31
Bulk density (gm/ml) 0.26 ± 0.23 0.26 ± 0.29 0.46 ± 0.37
Tapped density (gm/ml) 0.51 ± 0.42 0.37 ± 0.23 0.54 ± 0.26
Compressibility index (%) 49.01 ± 0.21 29.72 ± 0.31 14.81 ± 0.36
Hausner’s fraction 1.96 ± 0.31 1.42 ± 0.27 1.17 ± 0.31

11. Fig. 1 FT-IR Analysis Report of Verapamil
hydrochloride
2961.60 and 2838.88 (C-H streching vibration in methyl), 2579.65 and 2540.35 (aldihydic C-H stretching vibration),
2236.51 (C - N streching vibration), 1592.74, 1518.15 and 1464.32 (C=C in aromatic ring),
813.91and 768.08 (Meta substituted benzene).

12. Fig. 2 FT-IR Analysis Report of Verapamil
hydrochloride & Eudragit RSPO

13. Fig. 3 FT-IR Analysis Report of Verapamil
hydrochloride & HPMCK4M

14. Discussions
 Standard graph of Verapamil Hydrochloride in 0.1 N HCl showed good linearity.
Its ‘r2’ value is 0.9986
 The percentage of drug content was found to be 90–96%, which was within
acceptable limits (I.P. 1996).
 Micromeritic properties of the solid dispersions (SDs) and physical mixtures
(PMs) indicated a significant improvement of flowability.
 Favorable particle properties and the optimal presence of water diminish the
cohesiveness of the SDs and PMs, resulting in an increased bulk density and
enhanced flowability
 Micromeritic properties of the SDs and PMs such as angle of repose (23+ 0.31),
Carr’s index (14.81+ 0.36) and Hausner’s fraction (1.17+0.31) revealed that
they were well within the theoretical limit

15. Fig 4.Release profile of solid dispersions and
physical mixtures containing (HPMCK4M)
Zero Order Plot For VPH:HPMCK4M
2015105
Cum.%DrugRelease
120
100
80
60
40
20
0
-20
0
F1
F2
F3
F10
F11
F12
Time (hrs)

16. Fig 5.Release profile of solid dispersions and
physical mixtures containing (Eudragit RSPO)
2015105
Cum.%DrugReleas
Zero Order Plot For VPHRSPO
120
100
80
60
40
20
0
-20
0
F4
F5
F6
F13
F14
F15
Time (hrs)

17. Fig 6.Release profile of solid dispersions and
physical mixtures containing (Eudragit RSPO
and HPMCK4M)
time (hrs)
252015105
F7
F8
F9
F16
F17
F18
120
100
80
60
40
20
0
-20
0
ZeroOrderPlotForVPHRSPOHPMCK4M
Cum.%Drugrelease

18. Effect of combination of HPMCK4M and
Eudragit RSPO on drug release from SDs and
PMs
 Combination of the two selected polymers showed a synergistic effect in
retarding the release of the drug;
 hence selection of suitable proportion of the two polymers can be used to
optimize the release of drug.
 Drug release from PM followed Higuchi model kinetics and the ratio Drug:
Eudragit RSPO: HPMCK4M (1:7:0.5) sustained release only up to 8 hrs.
 Koresmeyer & Peppas release exponent suggests that the release followed
Fickian diffusion mechanism.
 Similarly drug release from SDs followed Higuchi model kinetics and the ratio
Drug: Eudragit RSPO: HPMCK4M (1:7:0.5) showed release retardation up to 12
hrs.

19. Conclusion
 A systematic study involving preparation and evaluation of sustained release
solid dispersions of Verapamil hydrochloride using release retarding polymers
was made.
 PMs could sustain the release of drug only upto 8 hrs whereas In-Vitro release
profile suggested that the drug release has been extended with solid
dispersions (Drug: HPMCK4M) up to 16 hrs whereas solid dispersions (Drug:
Eudragit RSPO) up to 10 hrs and solid dispersions (Drug: Eudragit RSPO:
HPMCK4M) up to 12 hrs respectively.
 From the above research it may be concluded that HPMCK4M acts as a better
release retardant for the model drug.

20. References
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