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AASCIT Journal of Nanoscience

2015; 1(4): 50-59

Published online September 20, 2015 (http://www.aascit.org/journal/nanoscience)

Keywords In vitro,

Gentamicin,

SMEDDS,

Drug-Delivery,

Lipid,

Matrix

Received: August 13, 2015

Revised: September 7, 2015

Accepted: September 8, 2015

In vitro Evaluation of Gentamicin Coupled Self-Micro-Emulsifying Drug Delivery Systems (SMEDDS) Containing Softisan and Precirol as Lipid Matrix

Osonwa U. E.1, Nwabugwu C. K.

1, Ugoeze K. C.

2, *

1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical

Sciences, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria 2Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical

Sciences, University of Port Harcourt, Port Harcourt, Nigeria

Email address [email protected] (Ugoeze K. C.)

Citation Osonwa U. E., Nwabugwu C. K., Ugoeze K. C.. In vitro Evaluation of Gentamicin Coupled Self-

Micro-Emulsifying Drug Delivery Systems (SMEDDS) Containing Softisan and Precirol as Lipid

Matrix. AASCIT Journal of Nanoscience. Vol. 1, No. 4, 2015, pp. 50-59.

Abstract Gentamicin (GM), a broad-spectrum aminoglycoside antibiotic has insignificant small

intestinal absorption and this makes its oral administration impracticable. Its orally

administrable product in addition to parenteral delivery formula is necessary. In this

study in vitro evaluation of the stability of a self-micro-emulsifying drug delivery

systems (SMEDDS) prepared with varying ratios of softisan® 154 (S-154) and precirol

®

ATO 5 (P-5) and loaded with GM was carried out. Batches of SMEDDS were prepared

as: A1, S-154/P-5(1:1), A2, S-154/P-5(1:1), A3, S-154/P-5(1:1), A4, S-154/P-5(1:1)

loaded with 50, 100, 200 and 0 mg of GM respectively. Similarly batches B1,S-154/P-

5(1:2), B2,S-154/P-5(1:2), B3,S-154/P-5(1:2), B4,S-154/P-5(1:2) and C1,S-154/P-5(2:1),

C2,S-154/P-5(2:1), C3,S-154/P-5(2:1), C4,S-154/P-5(2:1) were prepared. The micro-

particles yield, time dependent particle size, pH, thermal analysis, encapsulation

efficiency and in vitro antimicrobial efficacy of the SMEDDS were investigated. Batch

B3, S-154/P-5(1:2) gave the highest yield of micro-particles while those of B1, S-154/P-

5(1:2) and C2, S-154/P-5(2:1) respectively were the most stable. Between 7 and 60 days,

B1, S-154/P-5 (1:2), B2, S-154/P-5 (1:2), B3, S-154/P-5 (1:2), C1, S-154/P-5 (2:1) and

C2, S-154/P-5 (2:1) were stable in their pH. Batch B3, S-154/P-5 (1:2) presented with

higher encapsulation efficiency as well as thermostability. The highest inhibition zone

diameter (IZD) of 14 mm was obtained with C3, S-154/P-5(2:1). This compared to A3,

S-154/P-5(1:1) and B3, S-154/P-5(1:2) with IZDs of 9 and 12 mm respectively. The

formulations containing softisan and precirol in the ratio of 1:2 and 2:1 respectively were

most stable in pH, particle size and thermostability and may likely be useful for oral

administration.

1. Introduction

Over 60 % of drug products are formulated for oral use signifying its dominance in

drug therapy. Though, this route of drug administration is often preferred due to its

convenience, high patient compliance, simpler production procedures and lower cost of

production (1, 2). Its limitations abound due to gastrointestinal permeability, metabolism

and elimination of drugs by the liver or gastrointestinal mucosa (first-pass effect), being

AASCIT Journal of Nanoscience 2015; 1(4): 50-59 51

that only those compounds that are stable in the

gastrointestinal tract can be administered orally (3). The oral

route has therefore been used for mainly non-peptide drugs.

Delivery of a drug by oral route is predominantly restricted

by pre-systemic degradation and poor penetration across the

gut wall. The oral delivery of lipophilic drugs present a major

challenge because of the low aqueous solubility (4, 5). It has

been stated that the primary mechanism of action which leads

to improved bioavailability is usually avoidance or partial

avoidance of slow dissolution process which limits the

bioavailability of hydrophobic drugs from conventional solid

dosage forms (6). Ideally, these novel formulations allow the

drug to remain in dissolved state throughout the transit over

the gastrointestinal tract. There are different categories of

vehicles, which can be selected to prepare a lipid carrier.

Such formulations can be used as oral liquids or can be

formulated into various types of capsules. The finished

product is then administered to the patient as a solid dosage

form (7). The modified release drug delivery systems are

advanced approach or formulation technologies for

transporting a pharmaceutical component in the body as

needed to achieve the intended safe desired therapeutic effect.

Categories of modified release drug delivery systems include

delayed release, sustained release, site-specific targeting,

receptor targeting, etc. Sustained release drug delivery

system include any drug delivery system that achieves slow

release of drug over an extended period of time (8). Over

recent years, much attention has been focused on lipid micro-

emulsion formulations, with particular emphasis on liquid

self-micro-emulsifying (SMEDDS) and self-emulsifying

drug delivery systems (SEDDS) to improve the oral

bioavailability of poorly water-soluble drugs (9-11). The

method of drug delivery where there is spontaneous

emulsification is known as self-micro-emulsifying drug

delivery system (SMEDDS). Formulations of self-

emulsifying drug delivery systems for lipophilic drugs has

been reported showing that isotropic mixtures of oil,

surfactants, solvents, and co-solvents/surfactants can be used

for the design of formulations in order to improve the oral

absorption and bioavailability of highly lipophilic and

charged hydrophilic compounds like aminoglycosides, e.g.

gentamicin (12, 13).

Homolipids are esters of fatty acids with various alcohols.

Lipid-based formulations have been shown to enhance the

bioavailability of drugs administered orally (14-17).

Widening availability of lipidic excipients with specific

characteristics offer flexibility of application with respect to

improving the bioavailability of poorly water-soluble drugs

and manipulating their release profiles (18). Lipids may have

considerable clinical impact. Ingested food containing lipids

can significantly alter postprandial drug absorption and its

bioavailability (19, 20).

Gentamicin (GM) is a broad-spectrum bactericidal

aminoglycoside antibiotic, produced by fermentation of

Micromonospora purpura or M. echinospora. It was

introduced in 1958 and showed better effectiveness than

earlier aminoglycosides being less susceptible to bacterial

resistance. GM is effective against wide variety of serious

bacterial infections caused by susceptible gram-negative and

some gram-positive aerobic bacteria. In addition, it is also

effective against hard to kill pseudomonas species. It is

highly water soluble and shows poor oral absorption and

poor protein binding. It is distributed well in body fluids, but

poorly in many tissues. Thus it is only effective at treating

aerobic bacteria.

GM is also absorbed well from denuded skin and the

peritoneum, pleural cavity, and joints. The drug is eliminated

renally unchanged (21-23). It is a bactericidal antibiotic that

works by binding the 30S subunit of the bacterial ribosome,

interrupting protein synthesis. Like all aminoglycosides,

when gentamicin is given orally, it is not systemically active.

This is because it is not absorbed to any appreciable extent

from the small intestine. It is administered intravenously,

intramuscularly or topically to treat infections. It appears to

be completely eliminated unchanged in the urine (24) Due to

its high solubility and high polarity, it does not cross cell

membranes efficiently, which is an important drawback for

the therapy of intracellular infections such as brucellosis, due

to the low antibiotic levels achievable inside infected cells.

Several reports indicate that gentamicin is more active in

vitro against clinical isolates of Brucella than streptomycin.

The ototoxicity and nephrotoxicity of GM pose major

problems in its clinical applications (25). The broad-spectrum

antibacterial properties as well as clinical applications and

notable side effects of gentamicin are well documented (21,

26, 27).

Oral drug delivery is the most desirable and the preferred

method of administrating therapeutic agents. In addition, the

oral medication is generally considered as the first choice for

investigation in the discovery and development of new

pharmaceutical formulations due to convenience in

administration, patient compliance and cost effective

manufacturing process. The overall process of oral delivery is

frequently impaired by several physiological and

pharmaceutical challenges that are associated with the

inherent physicochemical nature of the drugs and/or the

variability in GI condition such as pH, presence of food,

transit times, as well as enzymatic activity in the GI tract (28).

Like all aminoglycosides, when GM is given orally, it is not

systemically active since it is not absorbed to any appreciable

extent from the small intestine. This poor bioavailability is as

a result of its highly charged nature, size and acid instability.

It has been administered intravenously, intramuscularly or

topically to treat infections and appears to be completely

eliminated unchanged in the urine (24).

This study was carried out to formulate and evaluate

SMEDDS that contain admixtures of softisan® 154

(designated as S-154) and precirol® ATO 5 (designated as P-5)

and tween 80 loaded with GM to determine the stability of

their formulations. Tween 80, a non-ionic surfactant was

chosen for this work because of its ability to form

spontaneous emulsion with the homolipid. It is considerably

52 Osonwa U. E. et al.: In vitro Evaluation of Gentamicin Coupled Self-Micro-Emulsifying Drug Delivery Systems (SMEDDS)

Containing Softisan and Precirol as Lipid Matrix

less toxic compared to other ionic surfactants and absence of

charge greatly reduces its drug interaction potential. The best

proportion of S-154 and P-5 used in the product design was

determined in order to possibly improve the oral

bioavailability of gentamicin. S-154, a hydrogenated palm oil

(a triglyceride of C14-C18 fatty acids) is a white hard fat

with a neutral odour and taste. It is characterized by its

exceptional hardness at room temperature and sharp melting

point range of 53-58° C. The close proximity of melting and

solidification as well as stability against oxidation makes S-

154 suitable for formulating solid lipid micro-particles. P-5, a

glycerol distearate is a fine white powder of well controlled

particle size distribution with an indicative particle size of 50

µm. It is a high melting point lipid for use in the modified

release of oral solid dosage forms. In this work, softisan®

154 and precirol® ATO 5 were simply referred to as S-154

and P-5.

2. Materials and Methods

2.1. Materials

The following reagents were used as supplied: softisan®

154 (Peter Cremer, USA), precirol® ATO 5 (Gattefosse,

France), tween 80 (Sigma-Aldrich, Brazil), Mueller-Hinton

agar (Sigma Aldrich, Germany). Gentamycin sulphate was a

gift from Juhel Nigeria Ltd. The organism was obtained from

a stock culture of staphylococcus aureus in the laboratory of

the Department of Pharmaceutical Microbiology and

Pharmaceutical Biotechnology, Faculty of Pharmaceutical

Sciences, Nnamdi Azikiwe University, Awka, Nigeria.

2.2. Methods

2.2.1. Preparation of Lipid Matrix Using

Softisan and Precirol

Respective quantities of S-154 and P-5 as shown in Table

1 were weighed and melted together in a beaker at 70°C to

form the lipid matrix.

2.2.2. Preparation of SMEDDS

Each batch of the SMEDDS was prepared by mixing a

matrix-drug blend with aqueous dispersion of 1 ml of tween

80, all at 70 o C while stirring. This combination was injected

drop-wise from a 5 ml syringe and needle into propylene

glycol (a non-solvent) stirred at 1000 rpm. The SMEDDS

were filtered out using filter paper (Whatmann No. 1) and

dried for 72 h in a desiccator containing `fused calcium

chloride. This procedure was similar to a study by Schubert

and M¨uller Goymann (29). The weight of the SMEDDS

were calculated after drying to obtain the yield using the

equation below.

% Recovery = W1/W2 + W3 × 100 (1)

where, W1 is the weight (g) of SMEDDS formulated, W2 the

weight (g) of drug added and W3 is the weight (g) of

homolipid and tween 80 (g) used as the starting material.

2.2.3. Evaluation of the SMEDDS

Time-dependent particle size analysis

A 10 mg quantity of the SMEDDS was placed inside the

ring of the internally calibrated microscopic slide (objective

micrometre) and a drop of propylene glycol was added for a

clearer view. The slide was viewed under a binocular

microscope at a magnification of ×100. Different particles of

the SMEDDS from a particular batch were counted manually

since they were sizeable enough.

2.2.4. Time Dependent pH Study

The pH of 0.05 g dispersion of each of the twelve different

formulations in 50 ml distilled water was determined in

triplicates after 2, 7 and 60 days respectively using a pH

meter (Jenway, 3505).

2.2.5. Beer’s Plot for Gentamicin

Beer’s plot was obtained with the concentrations of

(0.001953, 0.0039, 0.007813, 0.0156, 0.0312, 0.0625, 0.125,

0.25, 0.5 mg %) of gentamicin.

Table 1. Formulation of batches of the SMEDDS.

Batch Code Weight of lipid matrix (g) Volume of tween 80(ml) GM (mg) Water q. s (ml)

A1, S-154/P-5(1:1) 5.0 1.0 50.0 50.0

A2, S-154/P-5(1:1) 5.0 1.0 100.0 50.0

A3, S-154/P-5(1:1) 5.0 1.0 200.0 50.0

A4, S-154/P-5(1:1) 5.0 1.0 0.0 50.0

B1, S-154/P-5(1:2) 5.0 1.0 50.0 50.0

B2, S-154/P-5(1:2) 5.0 1.0 100.0 50.0

B3, S-154/P-5(1:2) 5.0 1.0 200.0 50.0

B4, S-154/P-5(1:2) 5.0 1.0 0.0 50.0

C1, S-154/P-5(2:1) 5.0 1.0 50.0 50.0

C2, S-154/P-5(2:1) 5.0 1.0 100.0 50.0

C3, S-154/P-5(2:1) 5.0 1.0 200.0 50.0

C4, S-154/P-5(2:1) 5.0 1.0 0.0 50.0

2.2.6. Drug Content of the Formulated

SMEDDS

A 0.4 g quantity of each batch of the SMEDDS was placed

in a 100 ml volumetric flask and made up to 100 ml in water

and allowed to equilibrate for 24 h at 40 o

C in a thermo-

stated water bath with intermittent shaking. The solution was

later cooled to 0 °C in a refrigerator. It was filtered using a

membrane filter and analysed spectrophotometrically at 420

nm (Jenway, England). The drug concentration in each batch

was calculated with reference to Beer’s plot.


2.2.7. Drug Encapsulation Efficiency

The theoretical amount of the drug contained in the

SMEDDS were compared with the actual amount obtained

from the drug content studies to obtain the drug

encapsulation efficiency using the equation:

Encapsulation Efficiency (%) = ADC/TDC × 100 (2)

where, ADC is the actual drug content and TDC is the

theoretical drug content.

2.2.8. Thermal Analysis

This was conducted with the calorimeter, Netzsch DSC

204 FI (Phoenix, Germany). 1mg of the SMEDDS was

sealed in aluminium pan with a similar empty pan serving as

control. The equipment was calibrated with indium and

purged with nitrogen gas. The sample was heated at the rate

of 10°C/min from 30°C to 400°C under nitrogen flow rate of

20 ml/min followed by cooling back to 30°C at the same rate.

2.2.9. In vitro Antimicrobial Efficacy

The microbial inhibitory concentration (MIC) of the

gentamicin loaded in the SMEDDS was determined. A 0.2

mg of it was added to distilled water and made up to 2 ml.

Sterile test tubes were labelled 1-12. A 0.5 ml of distilled

water was introduced into four (4) other test tubes for each

batch. A 0.5 ml was collected from the stock of 0.2mg/2ml

and transfers were made using a two-fold serial dilution for

each batch. Culture of Staphylococcus aureus grown in

Mueller–Hinton broth was used. The broth matching the

turbidity of a 0.5 McFarland standard (1.5×10ˆ8 bacteria/ml)

was used to inoculate the Mueller–Hinton agar (50°C). The

mixture was plated onto a sterile glass plate kept horizontally

on an adjustable table-top in duplicates. The bacterial agar

was then allowed to solidify. Small wells (5 mm diameter)

were punched into the agar using a vacuum hole-puncher and

0.2 ml of dilutions of all the twelve batches of SMEDDS (0.1,

0.05, 0.025, 0.0125 mg/ml) was added into the respective

wells in duplicate. The plates were incubated for 48 hr. at

37°C.

3. Results and Discussion

3.1. Percentage Yield of the SMEDDS

The percentage yield of the SMEDDS increased as the

amount of GM increased from 50-200 mg in the respective

batches. Batch B3, S-154/P-5(1:2) loaded with 200 mg GM

produced the highest yield of 95.16 % (Table 2). This

proportion of matrix admixture generates complementary

structures, thus giving room for entrapment of high amount

of drug.

3.2. Time-Dependent Particle Size Analysis

The effect of storage period over particle size of the

SMEDDS is presented in Figure 1. It shows that for the

batches of formulations prepared with S-154/P-5 (1:1) and

containing 50, 100, 200 mg of GM respectively, particle size

increase was proportional to drug content especially with

batches A2, S-154/P-5(1:1) and A3, S-154/P-5(1:1)

containing 100 and 200 mg GM respectively which has the

highest particle sizes in the first 7 days. However, a

significant reduction in particle size was observed in the

same batches after 60 days. Though, a similar trend was

observed in the other formulations, batches B1,S-154/P-5(1:2)

and C2, S-154/P-5 (2:1) containing 50 and 100 mg GM

respectively were most stable as the instability of the

products increased with increasing amount of GM. This trend

may likely be due to extravasation of the drug from the

capsule and also an indication of instability. However,

particle size increase may be due to flocculation and

coalescence of particles while the reduction in particle size

may be due to extravasation (30, 31).

3.3. Time-Dependent pH Study

Figure 1. Effect of storage time on the particle size of SMEDDS.

Table 2. Percentage yield of the batches of SMEDDS.

Batch code Amount recovered (g) Amount yielded (%)

A1, [S-154: P-5(1:1)] 5.45 90.08

A2, [S-154: P-5(1:1)] 5.60 91.80

A3, [S-154: P-5(1:1)] 5.82 93.87

A4, [S-154: P-5(1:1)] 5.29 88.16

B1, [S-154: P-5(1:2)] 5.50 90.09

B2, [S-154: P-5(1:2)] 5.79 94.91

B3, [S-154: P-5(1:2)] 5.82 95.16

B4, [S-154: P-5(1:2)] 5.01 83.35

C1, [S-154: P-5(2:1)] 5.02 82.97

C2, [S-154: P-5(2:1)] 5.20 85.25

C3, [S-154: P-5(2:1)] 5.61 90.32

C4, [S-154: P-5(2:1)] 4.92 82.00

The pH of the batches of SMEDDS formulated with S-

154/P-5 (1:1) and S-154/P-5 (1:2) decreased over time



(Figure 2). This could be attributed to rancidity of lipids.

Oxidation of free fatty acids which were present in the

matrix caused reduction in pH making them acidic (32).

However, the changes were more pronounced in the

formulations prepared from S-154/P-5(1:1). On the other

hand, increase in pH was noted over storage time in the

batches of S-154/P-5 (2:1) loaded with 50, 100, 200 and 0

mg of GM respectively. The pH of the batches B1, S-154/P-

5 (1:2); B2, S-154/P-5 (1:2); B3, S-154/P-5 (1:2); C1, S-

154/P-5 (2:1) and C2, S-154/P-5 (2:1) were stable between

7 and 60 days.

3.4. Drug Content Analysis and

Encapsulation Efficiency

The encapsulation efficiency and actual drug content of the

entire formulations were shown in Table 3. Low values were

generally observed. This may be due to the hydrophilic

nature of GM and its insolubility in a hydrophobic matrix.

However, those batches prepared with S-154/P-5(1:2),

especially B3, S-154/P-5(1:2) showed the highest

encapsulation efficiency, having entrapped more drug than

other batches.

3.5. Thermal Analysis

The thermograms for pure GM, the matrix prepared from

S-154/P-5(1:1), batch A3,S-154/P-5(1:1), matrix constituted

from S-154/P-5(1:2), batch B3,S-154/P-5(1:2), matrix

prepared from S-154/P-5(2:1) and batch C3, S-154/P-5(2:1)

are shown in Figures 3-9 respectively. Batch A3, S-154/P-

5(1:1) lost a peak while batch C3, S-154/P-5(2:1) lost two

peaks significant in the thermograms of the pure GM. These

may be indication of interactions. There was broadening of

the GM peak at 78.9oC in batch B3, S-154/P-5(1:2) which

merged with the peak of the matrix constituted from S-154/P-

5(1:2). Other peaks were retained but there was a shift of the

melting point of GM from 249.1 to 99.5 o

C. This is

suggestive of molecular rearrangement and possible change

in crystal lattice structure. Thus, batch B3, S-154/P-5(1:2)

could be regarded as the most stable.

Figure 2. Chart representing time-dependent pH study.


Table 3. Actual drug content and encapsulation efficiency.

Batch code Theoretical drug content (mg) Actual drug content (mg) Encapsulation efficiency (%)

A1,[S-154: P-5(1:1)] 50 16 32

A2, [S-154: P-5(1:1)] 100 40 40

A3, [S-154: P-5(1:1)] 200 70 35

B1,[S-154: P-5(1:2)] 50 17 34

B2,[S-154: P-5(1:2)] 100 36 36

B3,[S-154: P-5(1:2)] 200 82 42

C1,[S-154: P-5(2:1)] 50 17.5 35

C2,[S-154: P-5(2:1)] 100 30 30

C3,[S-154: P-5(2:1)] 200 80 40

3.6. In vitro Antimicrobial Efficacy

The results of the antimicrobial screening are shown in

Tables 4 and 5. The highest inhibition zone diameter (IZD) of

14 mm was recorded in batch C3, S-154/P-5(2:1). This

compared to batches A3, S-154/P-5(1:1) and B3, S-154/P-5

(1: 2) with IZDs of 9 and 12 mm respectively. This activity

noted with formulations prepared from S-154/P-5(2:1) series

may be due higher drug release lower particle sizes obtained

from these batches (Fig. 1).

Figure 3. DSC thermogram of pure gentamicin sulphate.

Figure 4. DSC thermogram of the matrix prepared with S-154/P-5(1:1).



Figure 5. DSC thermogram of batch A3, S-154/P-5(1:1) loaded with 200 mg of GM.

Figure 6. DSC thermogram of matrix prepared with S-154/P-5(1:2).

Figure 7. DSC thermogram of batch B3, S-154/P-5(1:2) loaded with 200 mg of GM.


Figure 8. DSC thermogram of matrix prepared with S-154/P-5(2:1).

Figure 9. DSC thermogram of batch C3,S-154/P-5(2:1) loaded with 200 mg of GM.

Table 4. Activity of pure gentamicin against Staphylococcus aureus.

Sample Inhibition zone diameter (IZD) (mm)

Gentamicin 20µg/ml 10µg/ml 5µg/ml 2.5µg/ml

22 15 6 4

Table 5. Activity of SMEDDS against Staphylococcus aureus.

Batch IZD (mm)

0.1 mg/ml 0.05 mg/ml 0.025 mg/ml 0.0125 mg/ml

A1,S-154/P-5(1:1) 7 0 0 0

A2, S-154/P-5(1:1) 9 7 5 0

A3, S-154/P-5(1:1) 9 6 4 0

A4, S-154/P-5(1:1) 0 0 0 0

B1,S-154/P-5(1:2) 6 2 0 0

B2, S-154/P-5(1:2) 7 5 0 0

B3, S-154/P-5(1:2) 12 9 7 3

B4, S-154/P-5(1:2) 0 0 0 0

C1,S-154/P-5(2:1) 5 3 0 0

C2,S-154/P-5(2:1) 4 0 0 0

C3,S-154/P-5(2:1) 14 12 8 5

C4,S-154/P-5(2:1) 0 0 0 0



3.7. Conclusion

Having formulated respective batches self-micro-

emulsifying drug delivery systems (SMEDDS) impregnated

with gentamycin from various ratios of S-154 and P-5, batch

B3, S-154/P-5(1:2) that was loaded with 200 mg of GM gave

the highest percentage yield. Batches B1, S-154/P-5(1:2) and

C2, S-154/P-5(2:1) were the most stable in terms of particle

size. Batches B1, S-154/P-5(1:2); B2, S-154/P-5(1:2); B3, S-

154/P-5(1:2); C1, S-154/P-5(2:1) and C2, S-154/P-5(2:1)

were stable in pH over time. Batch B3, S-154/P-5(1:2)

produced the highest encapsulation efficiency. The stability

of batch B3, S-154/P-5(1:2) was more pronounced

considering its DSC thermogram (Fig. 7). Themograms of

the batches prepared with S-154/P-5 (1:1) or S-154/P-5(2:1)

presented with interactions characteristics of loss of peaks

significant in the thermogram of pure gentamicin sulphate.

Batches of SMEDDS formulated with S-154/P-5(2:1)

produced the highest antimicrobial activity against S. aureus

than those in the S-154/P-5(1:2) series. The in-vitro

evaluations carried out on the SMEDDS loaded with

gentamicin sulphate proved that batches of formulations

containing softisan and precirol in the ratio of 1:2 and 2:1

respectively were the most stable over time.

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