E

Presented by:

Shashank SoniAssistant Professor

School of Pharmaceutical SciencesSardar Bhagwan Singh PG Institute of Bio Medical Sciences

and Research, DehradunHow to cite this article:http://www.revistafarmacia.ro/201701/art-23-Soni_Verma_INDIA_142-152.pdf

The purpose of the present investigation is to study the effect of incorporation of Gelucire

39/01 and 50/13 on encapsulation efficiency and release of water soluble and insoluble drugs

(Metronidazole , log P= 0.0 and Norfloxacin, log P= 1.5) from floating alginate beads.

Floating beads (with or without drug) were prepared by extruding dropwise with the help of a

hypodermic needle an emulsion of sodium alginate (SA) with Gelucire 39/01 and 50/13

containing CaCO3 into CaCl2 solution prepared in 10% v/v acetic acid. Beads formed

instantaneously were cured for 10 min in the gelation medium at 370C. Prepared beads

showed excellent buoyancy in vitro, significantly (p<0.05) improved encapsulation efficiency

and sustained release of model drugs. In conclusion, these beads may form a potential

stomach site specific drug delivery system for the delivery of both water soluble and insoluble

drugs with absorption window in upper gastrointestinal tract.

Key words: Alginate beads, floating drug delivery systems, Gelucire, Metronidazole,

Norfloxacin

Floating Ca++ induced alginate beads have been developed in recent years

as a unique vehicle for stomach specific drug delivery. These beads can be

frequently produced by extruding a solution of SA containing a gas-

generating agent (CaCO3 or NaHCO3) into a divalent (Ca++ ) crosslinking

solution in acetic acid (generally 10% v/v) .

However, these beads often suffers from poor drug loading due to drug

loss during preparation by leaching through the pores in the beads and/or

fast drug release in acidic medium. A number of efforts have been made in

past to overcome these demerits.

These include use of different gas-generating agents; incorporation of

vegetable oils and other additives into alginate beads. But these

modifications often lead to the systems which are difficult to reproduce or

scale up or not acceptable for human use due to presence of traces of

chemical crosslinker.

In our quest to search techniques to overcome the demerits of alginate

beads, we did extensive experimentation in our laboratory and investigated

the feasibility of combining Gelucire 39/01 and 50/13 with SA to produce

floating emulsion gel beads by ionotropic gelation with Ca++.

Although SA promptly formed the emulsion with Gelucire 39/01, the

reason for incorporating Gelucire 50/13 was to promote further

emulsification of SA with Gelucire 39/01 and to prevent the excessive

retardation of drug release due highly lipophilic nature of Gelucire 39/01.

The buoyancy to the beads was attributed to the use of CaCO3. The reason

for choosing the Gelucires as lipid phase was their excellent potential

against rancidity. The prepared Gelucire based emulsion gel beads are

expected to be superior to emulsion gel beads reported by various workers

in the respect that there would be no leakage of oil from the beads as

Gelucires are solid at room temperature.

Further, in most of the studies vegetable oils were used, which are

susceptible to oxidation, whereas, Gelucires are least susceptible to

oxidation.

In the present study, we prepared two sets of Gelucires based floating

emulsion gel bead formulations containing model drugs Metronidazole

(MTZ) and Norfloxacin (NFC) respectively.

The prepared bead formulations are expected to retard the release of

embedded drugs in the acidic environment of stomach with improved

encapsulation efficiency.

Selection and characterization of drug molecules (Metronidazole base

and Norfloxacin) by UV, FTIR, DSC analytical methods.

Selection of polymers and other excipient for formulation of floating

emulsion gel beads like Gelucire, Sodium alginate used in combination

or may be used alone.

Preformulation studies of polymers, excipient and drugs.

Formulation of emulsion gel beads by emulsion gellation technique.

• Characterization of emulsion gel beads by following parameters.

Study of drug-polymer interaction

Conformation of emulsion gel beads

Surface topography of gelled beads

Swelling index of the beads

Drug entrapment efficiency of the beads

In vitro drug release of the beads

Release Kinetics study of the beads

Analysis of Drugs

Fourier transforms infrared spectroscopy (FTIR)

Ultraviolet absorption for estimation of λmax.

Differential scanning calorimetry (DSC) study

Quantitative Estimation of Drugs

Determination of absorption maxima

Preparation of 0.1 N HCl Buffer pH 1.2

Media for Preparation of Standard Curve

Preparation of Standard Curve

Characterization of emulsion gel beads

Drug excipient interaction studies

Morphology and beads size determination

In vitro buoyancy estimation

In vitro release profile studies

Determination of Drug entrapment efficiency

Release kinetics of drug release by Zero order, First order, Higuchi role

model, Korsmeyer and peppas model

Materials

Metronidazole (MTZ) and Norfloxacin (NFC) was gifted by Simpex

Laboratories Kotdwar, India. Sodium alginate was purchased from Sigma-

Aldrich (St. Louis, USA). Gelucire 39/01 (waxy solid, melting point 39 0C,

HLB = 01) and 50/13 (melting point 500C, HLB = 13) was a gift from

Gattefosse SAS (St Priest, Cedex, France). Water used in the formulations

was of HPLC grade (Merck) and all other chemicals used were of

analytical grade.

MethodsPreparation of SA-Gelucire emulsion

The SA-Gelucire emulsion was prepared by mixing SA solution with a

mixture of molten Gelucires (39/01 and 50/13) with the help of a mechanical

stirrer at around 500 rpm for 5 min.Preparation of floating emulsion gel beads

Floating emulsion gel beads were prepared by (Table 1) by extruding an

emulsion of SA with Gelucire 39/01 and 50/13 containing CaCO3 (with or

without drug) with the help of 25 ml hypodermic syringe, into CaCl2 solution

(3%w/v in 10% v/v acetic acid) at room temperature (280C). The beads formed

instantaneously, were cured for 10 minutes in gelation medium at 37 0C with

mild agitation.

Prepared beads were separated by filtration, washed thrice with deionized

water and dried in an oven at 35 0C for 12 hours than kept in a desiccator

for another 12 hours before further experiments.

Further, floating alginate beads without Gelucires were also prepared for

comparison purposes. These beads were prepared by extruding dropwise a

solution of SA in deionized water containing CaCO3 (with or without

drug) into CaCl2 solution (3 %w/v in 10% v/v acetic acid) at room

temperature.

FORM. CODE

MTZ (mg)

NFC (mg)

SA (% w/v)

GELU. 39/01(mg)

GELU. 50/13 (mg)

CaCO3(% w/v)

Cacl2(% w/v)

M 100 1.5 1 3M1 100 1.5 50 16 1 3M2 100 1.5 30 10 1 3M3 100 1.5 25 5 1 3M4 100 1.5 20 5 1 3M5 100 1.5 30 5 1 3N 100 1.5 1 3N1 100 1.5 50 16 1 3N2 100 1.5 30 10 1 3N3 100 1.5 25 5 1 3N4 100 1.5 20 5 1 3N5 100 1.5 30 5 1 3

The most important property of alginates is their ability to form gels by

reaction with divalent cations such as Ca++. Monovalent cations and Mg++

do not induce gelation of alginates.

The gelation and crosslinking of SA are mainly achieved by the exchange

of Na+ from the guluronic acids with Ca++, and stacking of these guluronic

groups to form the characteristic egg- box structure. The Ca++ bind to the

α-L-guluronic acid blocks in a highly cooperative manner and the size of

the cooperative unit is more than 20 monomers. Each alginate chain

dimerizes to form junctions with many other chains and as a result gel

networks are formed .

The Ca++ reactivity to alginates is the result of Ca++ induced dimeric

association of G-block regions.

Figure 1. Egg box association of poly L- guluronate sequences of alginate and conversion of random coils to ribbon structures when cross linked with ca2+ ions.

When an emulsion of SA with Gelucires containing CaCO3 was extruded

into acidic CaCl2 solutions, porous gel beads were formed instantaneously

due to simultaneous gas-generation and ionotropic gelation in which

intermolecular cross-links were formed between the Ca++ and the

negatively charged COO- groups of SA.

The prepared beads were cured in the gelation medium for 10 min at 37 0C. It was observed that when the beads were prepared at room

temperature (280C), they sank rapidly and there was no floating of dried

beads. Therefore, we have experimented the preparation of beads at

different temperatures and as result 370C temperature was selected.

The preparation and curing at this temperature facilitated the diffusion of

acidic gelation medium inside the bead structure in order to expedite the

reaction between gas-generating agent and acetic acid present in gelation

medium. The dried beads obtained from this procedure exhibited

prolonged floating when placed on 0.1 M HCl.

The absorption maxima for the drug (MTZ) is determined by UV

spectrophotometer and was found to be 278 nm when scanned between

200-400nm as shown in fig:

Fig2: Absorption maxima of Metronidazole base in 0.1M HCl (pH 1.2)

The absorption maxima for the drug (NFC) is determined by UV

spectrophotometer and was found to be 278 nm when scanned between

200-400nm as shown in fig:

Fig 3: Absorption maxima of Norfloxacin in 0.1M HCl at 278 nm (pH 1.2)

S.N0. CONC. (mcg/ml)

ABS. (nm)

1 0 02 2 0.1013 4 0.1864 6 0.2775 8 0.3516 10 0.422

S.N0. CONC. (mcg/ml)

ABS. (nm)

1 0 02 2 0.1203 4 0.1784 6 0.2525 8 0.3086 10 0.368

Parameters for MTZ. Drug

Parameters for NFC. Drug

S.NO. PARAMETERS VALUES

1 Regression coefficient

0.9962

2 Intercept on Y-axis

0.012

3 Equation of line

Y=0.0422x+0.012

S.NO. PARAMETERS VALUES

1 Regression coefficient

0.9816

2 Intercept on Y-axis

0.0273

3 Equation of line

Y=0.0354x+0.0273

Figure 4. FTIR spectrums of Metronidazole and Norfloxacin

The FTIR spectra of pure MTZ (Fig. 3) exhibited bands appearing at 2951,

2848 and 3098cm-1 due to C-H stretching. The bands at 1536 and 1366 are

due to N=O asymmetrical and symmetrical stretching. The bands at 1268

and 3220cm-1 are due to C-O and O-H stretching. The band due to

characteristic C-N stretching was seen at 1157cm-1. Additionally

characteristic band of drug C=N stretching appeared at around 1480cm-1.

The FTIR spectra of pure NFC (Fig. 3) exhibit a band at 1033cm-1 due to

C-F stretching (mono fluorinated compound). The bands appearing at

1730 and 1617cm-1 due to C=O stretching of carboxylic and carbonyl

group respectively. The band at 1483 is due to –CH; deformation of –CH2.

The band at 1382cm-1 is due to the C-H bending, whereas bands at 3416,

2844 and 2553 cm-1 are due to O-H, C-H and N-H stretching vibrations

respectively.

Figure 5. FTIR spectrum of Sodium alginate

FTIR spectrum of sodium alginate (Fig 4) is attributed to its saccharide

structure. The bands at 1620 and 1415 cm-1 are assigned to asymmetric and

symmetric stretching bands of carboxylate groups. The bands at 3435 and

2928 cm-1 are assigned to O-H stretching and C-H stretching in –CH2.

Figure 6. FTIR spectrum of Gelucire 39/01 and 50/13

Gelucire are polyethylene glycol glycerides composed of mono-, di- and

triglycerides and mono- and diesters of polyethylene glycol (PEG). Gelucire

39/01 is glycerol esters of saturated C12-C18 fatty acids, whereas, Gelucire

50/13 is PEG-32 glyceryl palmitostearate. The FTIR spectrum of Gelucire

39/01 showed characteristic bands at 1105, 1464, and 1742 cm-1

corresponding to C-O , C-H vibration of CH2 and C=O stretching vibrations

of esters respectively. The bands at 2922, 2853 cm-1 are due to C-H str.

(asymmetric and symmetric). Whereas, the FTIR spectrum of Gelucire 50/13

showed characteristic bands at 1105, 1638 and 1738 cm-1 assigned to C-O

stretching of esters, C=C and C=O stretching vibrations. The bands at 2847,

2884, 2919 cm-1 are due to C-H stretching vibrations.

Figure 7. FTIR spectrum of Metronidazole and Norfloxacin formulations

The FTIR spectrum of blank floating calcium alginate beads without

Gelucires was also recorded along with MTZ and NFC loaded formulations

to provide aid in interpretation of drug-excipient interactions. The FTIR

spectra of blank floating calcium alginate beads without Gelucires exhibited

characteristic bands at 1550 cm-1 indicating involvement of COO- group in

coordination process with Ca++; 1748 cm-1 indicates that some COO- group of

the SA transformed into carboxylic group due to interaction with Ca++ and

3434 cm-1 indicating involvement of hydroxyl group with Ca++. The FTIR

spectrum of NFC loaded formulation showed characteristic bands at 1104,

1421, 1622, 1741, 2923, 2854 and 3438 cm-1, whereas, MTZ loaded

formulation exhibited characteristic bands at 1268, 1462, 1744, 2924, 2854,

3099, 3224 and 3428 cm-1. This suggests that all the major bands of drugs

were intact and there was no evidence of interaction.

Figure 8. DSC thermograms of Metronidazole and Norfloxacin

The DSC profile (Fig. 8) of NFC showed a sharp endothermic peak at

223.92 0C and an exothermic peak at 287 0C corresponding to the melting

point and degradation of NFC. The DSC profile (Fig. 8) of MTZ base

showed a sharp endothermic peak at 162.52 0C corresponding to the

melting point of drugs.

Figure 9. DSC thermograms of sodium alginate, Gelucire 50/13 and 39/01

The DSC thermogram of SA exhibited two endotherms at 146 and 210 0C,

corresponding to the dehydration of water and very slow melting of SA.

The DSC thermogram of Gelucire 39/01 showed two endothermic peaks at

35 and 44 0C, whereas , thermogram of Gelucire 50/13 showed (Fig. 9) a

broad endothermic peak at 46 0C.

The DSC thermogram of MTZ emulsion beads (Fig.9) bearing exhibited

three endothermic and one exothermic peak. The first endothermic peak

(very weak) at around 40 0C could be attributed to the melting of

Gelucires, whereas, the second endothermic peak (broad) at 69 0C could be

attributed to dehydration of water, whereas, the third endothermic peak at

160 0C could be attributed to the melting of MTZ. The exothermic peak at

246 0C could be attributed to the degradation of SA in the beads.

On the other hand, in the DSC thermogram of NFC emulsion bead

formulations, the melting endotherm of NFC is missing indicating intimate

mixing of NFC in the Gelucires-SA emulsion. The data obtained from the

thermal studies exclude the possibility of interaction between drug,

Gelucires and SA.

The scanning electron micrographs (SEM) of various MTZ and NFC

loaded floating emulsion beads are shown in Figure 8. The SEM results

revealed that NFC loaded floating emulsion beads were spherical in shape,

whereas, MTZ loaded floating emulsion beads were relatively irregular in

shape with rough outer surfaces (Fig 10).

The transverse section of both MTZ and NFC loaded floating emulsion

beads showed a large hollow cavity along with numerous smaller internal

pores (Fig 10), attributed to the use of gas-generating agent.

Upon contact with an acidic medium, CaCO3 effervesced, releasing CO2.

The released CO2 slowly diffused through the gel network due to high

viscosity of emulsion, with internal crosslinking of SA with released Ca++

producing a cross-linked three-dimensional gel network that restricted

further diffusion of CO2 and resulted in entrapment of released CO2 inside

the bead structure, thus, producing hollow cavity.

Figure 10. SEM images of MTZ and NFC loaded formulations at various magnifications. (a) Shape of NFC loaded emulsion beads (b) surface morphology of NFC loaded floating emulsion beads (c) transverse section of NFC loaded emulsion beads (d) Shape of MTZ loaded floating emulsion beads (e) surface morphology of MTZ loaded floating emulsion beads (f) transverse section of MTZ loaded floating emulsion beads

The buoyancy of the beads was not dependent upon the lipid phase, i.e.,

Gelucires, as the emulsion beads prepared without the use of gas generating

agent sank rapidly. On the other hand, emulsion beads prepared with gas-

generating agent remained buoyant on 0.1 M HCl for sufficiently long

duration of time. Both floating emulsion beads remained buoyant for upto 18

hours on 0.1 M HCl with no floating lag time. Whereas floating beads (M

and N) prepared without Gelucires floated for about 14 hours on 0.1 M HCl.

Upon contact with an acidic medium, the CaCO3 effervesced, releasing CO2.

The released CO2 was entrapped in the gel network producing buoyant

formulation and thus, prolonged floating of emulsion beads.

It was also observed that in case of MTZ loaded emulsion beads, at higher

concentration of Gelucire 50/13 in the emulsion (M1), % buoyancy of the

beads was decreased. This could attributed to the formation of

comparatively more viscous emulsion (M1 compared M2, M3, M4 and

M5) due to the more efficient emulsification. When this emulsion was

extruded dropwise into the acidic gelation medium, the formation of dense

interior of the beads restricted the complete reaction between gas-

generating and acetic acid present in the gelation medium.

However, this effect was not observed with NFC loaded emulsion beads.

The possible explanation for this observed difference could be the uniform

distribution of insoluble NFC in the emulsion. At higher Gelucire 50/13

concentration, although a viscous emulsion was formed but it seems that

NFC remained insoluble and uniformly distributed in the emulsion. This

might have resulted in the easy ingress of acetic acid present in the

gelation medium in to the emulsion due to somewhat porous interior

conferred by insoluble NFC, leading to complete reaction with gas-

generating agent and thus improved buoyancy (N1 compared to M1) of the

resultant beads.

The effects of various formulation parameters on the entrapment efficiency

of the prepared floating emulsion beads are depicted in Table 2.

BAR GRAPH REPRESENTING % E.E OF MTZ. FORMULATIONS BAR GRAPH REPRESENTING % E.E OF

NFC. FORMULATIONS

The entrapment efficiency of prepared MTZ loaded floating emulsion

beads varied from 63 to 82 % (Fig. 10), whereas, the entrapment efficiency

of NFC loaded floating emulsion beads ranged from 76-84 % (Fig. 10).

The floating beads prepared without Gelucires showed entrapment

efficiency, 41.32 % (M) and 51.64 % (N) respectively. There was

significant difference (p< 0.05) in entrapment efficiency between floating

emulsion beads and floating beads prepared without Gelucires. This

increase in entrapment efficiency could be attributed to the use of

lipophilic Gelucire 39/01 in the preparation of floating emulsion beads.

This observation is consistent with the findings of (Murata et al., 2001)

who reported increased MTZ entrapment efficiency of emulsion gel beads

compared to calcium alginate beads. Further, these authors reported

maximum MTZ entrapment (76 %) at 30 % oil concentration, whereas, in

our case maximum MTZ entrapment efficiency (82 %) was found at very

low Gelucires concentration (M4).

It was also observed that, in case of MTZ loaded floating emulsion beads,

as the concentration of Gelucire 50/13 was reduced in the emulsion, drug

entrapment efficiency of the emulsion beads increased significantly (M1

compared to M2, M3, M4 and M5, p< 0.05).

This could be attributed to the high HLB of Gelucire 50/13, which when used

in high concentration, as in case of formulation M1, not only reduced the

hydrophobicity of emulsion but also affected the aqueous solubility of MTZ,

which in turn resulted in comparatively easy diffusion of water soluble drug

through the beads during processing in warm (37 0C) acidic gelation medium.

However, this effect was not observed with NFC loaded emulsion beads. In this

case, it seems that, although the hydrophobicity of the emulsion was decreased

but high concentration of Gelucire 50/13 could not affect the aqueous solubility

of NFC, which retarded the diffusion of drug through the beads during

processing. However, NFC is reported to be an amphoteric molecule, whose

solubility increases as the pH of the medium is reduced to below 4, but this

effect was not observed with NFC loaded emulsion beads.

The in vitro drug release profiles of MTZ and NFC from floating emulsion

bead formulations carried out in 0.01 M HCl (pH 1.2) are shown in Figure

11and 12.

Figure 11. Release profile of Metronidazole base in 0.01M HCl (pH 1.2)

Figure 12. Release profile of Norfloxacin in 0.01M HCl (pH 1.2)

DRUG RELEASE STUDIES OF METRONIDAZOLE BASE The drug release from all the MTZ loaded formulations was significantly

extended (upto 12-16 hours) compared to conventional floating calcium

alginate (upto 3 hours) beads (p< 0.05, M compared to M1, M2, M3, M4

and M5). There was ‘burst’ MTZ release from conventional floating

calcium alginate beads with about 60% of drug was released within first

hour and entire MTZ was emptied at the end of second hour. However,

incorporation of Gelucire 39/01 resulted in decreased release rates of

MTZ. This observation is consistent with the findings of Murata et al, who

reported decreased MTZ release rates from emulsion gel beads. From

formulation M1, around 13, 51, 75 and 99 % MTZ was released at the end

of 1st, 8th, 12th and 15th hour.

Formulations M2, M3, M4 and M5 were prepared to study the effect of

different combinations of Gelucire 39/01 and Gelucire 50/13 on drug

release. From formulation M2, about 18, 50, 75 and 99 % MTZ was

released at the end of 1st, 6th, 11th and 15th hour. The MTZ release from

formulation (M2) was significantly fast (p<0.05) from formulation M1.

This could be attributed to the reduced hydrophobicity of the formulation

together with decreased solubilizing effect of Gelucire 50/13 on MTZ

solubility in aqueous medium. In case of formulation M3, concentrations

of both Gelucire 39/01 and 50/13 was further reduced which has resulted

in MTZ release rate which has almost similar to M2 and there was no

significant difference (p>0.05) in release rate.

In case of formulation M4, the Gelucire 50/13 concentration was kept

constant, whereas, concentration of Gelucire 39/01 was further reduced.

This has resulted in MTZ release rate which was significantly fast from

M2 (p<0.05, M2 compared to M4), with approximately 22, 48, 75 and 99

% MTZ was released at the end of 1, 4, 8 and 12 hour. In case of

formulation M5, Gelucire 39/01 concentration was increased while

Gelucire 50/13 concentration kept constant. The MTZ release rate was

significantly retarded with approximately 6, 51, 72 and 99 % MTZ was

released at the end of 1, 8, 11 and 16 hour, which was significantly

different (p<0.05) from formulations M2, M3 and M4.

DRUG RELEASE STUDIES OF NORFLOXACIN :- The drug release from all NFC loaded formulations was also significantly

extended (upto 12-16 hours) compared to conventional NFC loaded

floating calcium alginate formulation (upto 3 hours). Here also, the NFC

release from calcium alginate beads was very rapid with about 55 % NFC

was released at the end of 1st hour and almost entire drug was released at

the end of 3rd hour. From formulation N1, around 24, 50, 74 and 99 %

NFC was released at the end of 1st, 6th, 10th and 15th hour. As the fraction of

Gelucire 39/01 was reduced in the emulsion bead formulation (N2), NFC

release was significantly increased (p< 0.05), with 25, 49, 77 and 99 %

NFC was released at the end of 1st, 4th, 8th and 12th.

On the other hand reducing the amount of Gelucire 50/13, resulted in

significant retardation of NFC release (N3 and N5 compared to N2, p<

0.05). From formulation N4, around 30, 48, 79 and 99 % NFC was

released at the end of 1st, 3rd 7th and 10th hour which was significantly

different from formulation N3 and N5 (p<0.05), which released

approximately 20, ≈49, ≈73, 99 % NFC at the end of 1st, 7th, 10th and 16th

hour.

The in vitro release pattern of various formulations was analyzed by fitting

the dissolution data into various kinetic models (Table 3). In case of MTZ

loaded emulsion beads, It was observed the for the formulations M1, M2,

M3 and M4, the r2 values were higher when fitted to zero order kinetics,

which describes that the drug release rate from the formulations is

independent of the concentration of the drug . For formulation M5, the r2

values was higher when fitted to Higuchi model, which describes the

release from system, where the solid drug is dispersed in an insoluble

matrix, and the rate of drug release is related to the rate of drug diffusion.

The n values from drug release experiment ranged from 0.58-0.77,

indicated anomalous non-Fickian transport, which suggest that mechanism

and kinetics of drug release were dependent on the solubility of MTZ in

dissolution medium, with MTZ being predominantly released by diffusion

and anomalous behaviour resulting from the relaxation of macromolecular

polymeric chains in emulsion gel beads.

In case of NFC loaded emulsion beads, formulation N1, N3 and N5

followed zero order kinetics as evidenced by r2 values, which were higher

when fitted to zero order kinetics. Whereas, formulations N2 and N4,

followed Higuchi kinetics, as evidenced by r2 values. The n values from

drug release experiment ranged from 0.44-0.55, with formulations N1 and

N4 followed Quasi-Fickian diffusion and formulations N2, N3 and N5

followed anomalous non-Fickian diffusion.

FORM. CODE

ZERO ORDER (R2

VALUE)

FIRST ORDER(R2

VALUE)

HIGUCHI(R2

VALUE)

KORSMEYER- PEPPA’S(R2 VALUE)

n VALUE

M1 0.9954 0.7302 0.9106 0.9227 0.76

M2 0.9891 0.6188 0.9627 0.9269 0.60

M3 0.9791 0.5787 0.9781 0.9777 0.60

M4 0.9957 0.7915 0.9107 0.9897 0.77

M5 0.9742 0.5548 0.9839 0.9974 0.58

TABLE 3 RELEASE KINETICS OF MTZ FROM FABRICATED GEL BEADS

FORM. CODE

ZERO ORDER (R2

VALUE)

FIRST ORDER(R2

VALUE)

HIGUCHI(R2

VALUE)

KORSMEYER- PEPPA’S(R2

VALUE)

n VALUE

N1 0.9739 0.5321 0.9709 0.9829 0.44

N2 0.9641 0.5289 0.9894 0.9906 0.52

N3 0.9846 0.5735 0.9741 0.9914 0.55

N4 0.9525 0.5195 0.9926 0.9976 0.48

N5 0.9896 0.5927 0.9643 0.9802 0.55

In this study, we have prepared Gelucire based floating emulsion gel beads

formulations and examined their drug encapsulation efficiency and release

characteristics by loading water soluble (MTZ) and water insoluble drugs

(NFC) separately.

Prepared beads showed high drug encapsulation efficiency; excellent

buoyancy and released the model drugs MTZ and NFC gradually in 0.1 M

HCl. These properties are not only applicable to the sustained release of

the drugs with absorption window in the upper GIT but also to the stomach

specific drug delivery.

These beads appears to be superior to previously reported emulsion gel

bead systems as the lipid phase (Gelucire 30/01 and 50/13) used is least

susceptible to rancidity and also there will be no leaking of lipid phase as it

is solid even at temperature upto 300C.

We propose that the prepared alginate based emulsion gel beads thought to

be able to sustain the release of both hydrophilic and hydrophobic drugs

over 12 h, while remaining afloat in gastric fluid.

I am very thankful to my guide Prof. Anurag Verma and all the faculty

members of IFTM, Moradabad, I would also like to extreme my special

votes of thanks to CSIF; Jamia Hamdard University, Department of

Chemistry and Department of Textile technology; IIT New Delhi (India)

for the characterization of my samples during dissertation work. I am also

thankful to Dr. Alok Mishra, COO, Simpex laboratories, India and my gift

samples supplier Gattefosse, France for supplying the samples in time.

This presentation is for knowledge and information only.

This research work freely available and cite this article as

Shashank Soni, Navneet Verma, Anurag Verma*, Jayanta K Pandit.

Gelucire Based Floating Emulsion Gel Beads: A Potential Carrier for

Sustained Stomach Specific Drug Delivery. FARMACIA. 65 (1): 142-152

(2017). ISSN: 0014-8237. http://www.revistafarmacia.ro/201701/art-23-Soni_Verma_INDIA_142-152.pdf