INTRODUCTION:

The majority of new drugs exhibit poor aqueous solubility, which affects their low bioavailability after oral delivery. Many strategies have been described to increase the dissolution rate of drugs by reducing their particle size and salt formation, using surfactants, cyclodextrins, liposomes or nanoparticles^1–4. A relatively new approach for poorly soluble drugs is lipid-based formulations, particularly self-emulsifying drug delivery systems (SEDDS)^5,6.

SEDDS are isotropic mixtures of oils and surfactants with or without co-surfactants, which act as lipid-based formulations after oral application in aqueous gastrointestinal fluid and upon gentle agitation can form an oil-in-water emulsion^7–10.

SEDDS technology was employed to increase solubility and consequently the bioavailability of many poorly water soluble drugs such as phyllanthin, celastrol, ketoprofen, indomethacin and hydrocortisone^11–14. SEDDS as liquid formulations have several disadvantages such as low drug loading capacity, drug leakage, low stability, and few choices of dosage forms. To overcome these limitations, liquid SEDDS (L-SEDDS) can be transformed to solid dosage forms by using different methods (filling capsules with liquid or semi-solid SEDDS, adsorption to solid carrier, melt granulation, spray drying, melt extrusion or nanoparticle formation)^15,16. Solid self-emulsifying drug delivery systems (S-SEDDS) combine the advantages of liquid lipid formulations with those of solid dosage forms such as higher stability and longer period of storage^17,18. S-SEDDS could be formulated in the form of self-emulsifying capsules, pellets/tablets, micro/nano-particles, suppositories or dry emulsions.

Most of the drugs at the market and New Chemical Entities (NCEs, approx. 75%) from the discovery pipeline are poorly water-soluble, it has never been so important for formulation scientists from academia and pharmaceutical industries to work on improving solubility. Nowadays, there are many challenges associated with formulating pediatric and Geriatric medicines for developing countries and the demand of pediatric and Geriatric medicine still remains at large. Dolutegravir Sodium (DLT) an antiretroviral drug used in various countries for the treatment of HIV infection. Pediatric and Geriatric patients need different oral dosage forms than adults due to differences in swallowing capabilities, taste likings, and dosage requirement. Pediatric patients need new modified dosage forms to fulfill recommended dosing treatments due to age differences when compared to another age group. However, adsorption onto solid carriers such as using MCC grade material is a very recent approach and a limited number of works has been done till now. After the conversion of liquid SEDDS into solids, free flowing powders have flexibility (ease of processing) in designing and developing solid dosage forms (easy to encapsulate the powder) as well as the reduction of intra- and inter-subject variability of drug dissolution profiles, thus lead to improvements in drug safety and efficacy. Bitter drugs are really very difficult for patient to take in oral dosage form, especially by pediatric and Geriatric patients. So, new Doshion Pharma grade polymer (Doshion P-544 DS), designed specifically mask the taste of drug was used in the formulation of tablet. This research project is mainly focused on the development of a flexible dosage form suitable for oral administration of Dolutegravir Sodium to pediatric and Geriatric patients.^19-21

MATERIALS AND METHODS:

Materials:

Dolutegravir Sodium was kindly donated by Emcure Pharmaceutical Ltd, Hinjewadi, Pune. Capmul MCM was obtained from Abitech Corporation, U.S.A., Cremophore RH40, Tween 80 and Tween 20 was procured from BASF, Mumbai, and Propylene glycol was obtained from Pure Chem Lab, Pune. Aerosil 200 was obtained from Oxford Laboratory Reagent, Mumbai and Neusilin US2 was obtained from Fuji Chemical Industry Co. Ltd., Japan. Doshion P-544 DS from Doshion Water Solution Private Limited, Ahmadabad. All other chemicals were of analytical grade. All other chemicals were of analytical grade.

Methods:

Solubility study:

The solubility of Dolutegravir Sodium in various oils (Capmul MCM, Isopropyl myristate, Aniseed oil, Oleic acid, Castor oil, and Olive oil), surfactants (Cremophore RH 40, Tween 20, Tween 80, and Span 20) and co-surfactant (PEG400, Transcutol HP, and Polyethylene glycol) it was determined. In a vial, 2ml of required solvent and excess quantity of the drug was added. The mixture was removed, filtrate and analyze by using UV spectrophotometer. All measurements were done in triplicates²².

Preliminary screening of surfactants for their emulsification ability:

Different surfactants were screened for emulsification ability according to the method described by Date and Nagarsenker (2007). Briefly, surfactant to oil in the ratio of 1:1 was mixed (300mg of the surfactants, Cremophore RH 40, Tween 20, Tween 80, and Span 20 were added to 300mg of the oily phase). The mixture of 50mg was diluted with distilled water and the % transmittance was evaluated at 638.2nm by using UV-spectrophotometer. Emulsions were furthermore observed visually for any turbidity or phase separation.

Preliminary screening of co-surfactants:

The selected oily phase and surfactant were used for further screening of the co-surfactant for their emulsification ability in the ratio of 3:2:1 of oil, surfactant, and co-surfactant respectively (it gives 1:1 ratio of Oil to S/Comix) Mixtures of 100mg of co-surfactant, 200mg surfactant and 300mg oil were prepared and evaluated similarly as above.

Construction of Pseudo ternary phase diagram:

The pseudo ternary phase diagram is a useful and important tool to study the extent of the microemulsion region and phase behavior. The pseudo-ternary phase diagrams were constructed by the water titration method. Add dropwise water to the homogenous liquid mixture of oil, surfactant, and co-surfactant, at ambient temperature (water titration method). The Pseudo ternary phase diagram can be represented in a triangular format (triangle) which has three coordinates. Each coordinate represents one component of the microemulsion system viz.

(1) Oil phase

(2) Surfactant Co-surfactant phase (Smix)

(3) Aqueous phase.

The pseudo ternary phase diagram is constructed to obtain the concentration ranges of components that can result in a large existence area of a microemulsion. At desired (ratio of surfactant to co-surfactant) value (1:1, 2:1, 3:1) Smix and oil were mixed at ratio of 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1 and 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1 in pre-weighed vial. To the resultant mixtures, water was added dropwise till it forms a clear or slightly bluish appearance, and easily flowable o/w microemulsion. A slightly less clear system, which had a bluish-white or bright white appearance, was defined as an emulsion. No attempt was made to find out other regions except the boundary of the microemulsion region in the ternary phase diagram. After identifying the highest microemulsion region at the desired Smix value, that value was put in Design-Expert software version 8 (Stat-Ease, Inc., Minneapolis, MN, trial version) to prepare liquid SEDDS. The phase diagram was constructed by using Central Composite Design Software (MN, USA, Trial version)²³.

Preparation of Liquid Self Emulsifying Formulation Loaded With Dolutegravir Sodium Using Central Composite Design:

Accurately weighed Dolutegravir Sodium and selected excipients Capmul MCM, Tween 80, and Propylene glycol were added to the vial and mixed using a magnetic stirrer for 15 min to aid mixing. Further, the formulations were warmed on a water bath at 40⁰C to help insolubilization. The formulations were observed for isotropic and were stored at room temperature until further analysis²⁴.

Characterization of formulations^21-25

Transmission electron microscopy:

For visual observation optimized batch of liquid SEDDS (F5) was subjected to transmission electron microscopy (TEM). The image was taken with transmission electron microscope.

Transmittance test:

The transmittance of each sample was measured at 638.2 nm.

Determination of self-emulsification time:

A quantity of 1ml of each formulation was added to 900 ml of distilled water under continuous stirring (50rpm) using USP dissolution test apparatus-II at 37±0.5ºC. The emulsification time was recorded in seconds.

Globule size determination:

Mean globule size and the polydispersity index of the resulting emulsions were determined by using photon correlation spectroscopy (Nanophox, Sympatec, Germany). The sample temperature was set at 25°C and detection was carried out at a scattering angle of 90°.

Determination of zeta potential:

The zeta potential was measured by using photon correlation spectroscopy.

Preparation of solid SEDDS:

The optimized liquid SEDDS formulation (F5) was converted into free-flowing powders by using adsorbents like aerosil 200 and Neusilin US2. The optimized liquid SEDDS was added dropwise to the solid adsorbent and mixed by using mortar and pestle.^{26, 27}

Solid State Characterization of S-SEDDS:

Differential Scanning Colorimetry (DSC):

Thermal analysis of pure drug and optimized S-SEDDS was carried out by using differential scanning calorimeter (DSC). The heating rate of 10°C/min. was employed in the temperature set from 20°C to 200°C, under an inert environment using nitrogen.

Powder X-Ray Diffraction (PXRD) analysis:

Powder X-ray diffraction (PXRD) study was studied by using an X-ray diffractometer with Cu-K𝛼 radiation (Voltage 40kV and the current 30mA). The scanning angle ranged from 5 to 25⁰ of 2θ.

Formulation and development of solid self-emulsifying drug delivery system (S-SEDDS) tablets:

The S-SEDDS tablets were prepared by using various superdisintegrants like sodium starch glycolate, Crosscarmellose sodium and Crospovidone (PPXL) at different concentrations by direct compression method as shown in Table 1. Accurately weighed S-SEDDS mixture, Superdisintegrants, Povidone, Microcrystalline cellulose, Mannitol and Doshion P-544 DS all material were passed through 40# screen and other ingredients Aspartame and Sodium Stearyl Fumarate were passed through 60 # screen prior to mixing and after this both powder mixture was mixed in blender and collect. Mixed final powder were compressed into tablets by using a rotary tablet machine.³⁰

Formulation and development of solid self emulsifying drug delivery system (S-SEDDS) tablets:

The 3²Full factorial design was applied for the tablet S-SEDDS formulation of Dolutegravir Sodium. The composition is as shown below:

Table 1: Formulation of 3²factorial design for S-SEDDS

Composition of Dolutegravir sodium S-SEDDS formulations
Ingredients mg/tab	F1	F2	F3	F4	F5	F6	F7	F8	F9
SSEDDS	50	50	50	50	50	50	50	50	50
Crosscarmellose sodium (Ac-Di-Sol)	3	---	---	7.5	---	---	12	---	---
Sodium Starch Glycolate	---	3	---	---	7.5	---	---	12	---
Crospovidone (PPXL)	---	---	3	---	---	7.5	---	---	12
Microcrystalline Cellulose	18	18	18	18	18	18	18	18	18
Mannitol (Pearitol 25C)	60.4	60.4	60.4	53.28	53.28	53.28	48.78	48.78	48.78
Povidone (PVPK-12)	7.5	7.5	7.5	7.5	7.5	7.5	7.5	7.5	7.5
Doshion P-544 DS	7.5	7.5	7.5	7.5	7.5	7.5	7.5	7.5	7.5
Aspartame	0.6	0.6	0.6	0.6	0.6	0.6	0.6	0.6	0.6
Sodium Stearyl Fumarate	3	3	3	3	3	3	3	3	3
Total	150	150	150	150	150	150	150	150	150

Evaluation of tablets^31,32

Hardness:

The hardness of the tablet of each formulation was determined by using the Monsanto Hardness tester.

Thickness:

The thickness was measured by placing the tablet between two arms of the Digital Vernier calipers.

Friability:

Roche friabilator was used to determine the friability by using the following formula.

Loss in weight

% Friability = -------------------------------- x100

Initial weight

Uniformity of weight:

According to Indian Pharmacopoeia procedure, the average weight of the tablet was determined from the collective weight.

Drug content:

The accurate weight of powder was dissolved in a suitable quantity of intestinal buffer pH 6.8 containing 2.5% SLS at 50rpm maintained at 37±0.5°C using the USP type II dissolution apparatus. The solution was filtered suitably diluted and the drug content was analyzed using a UV-Visible spectrometer at 259.8nm.

In-vitro drug release study:

The quantitative in vitro release test was performed in 900ml of intestinal buffer pH 6.8 containing 2.5% SLS at 50rpm maintained at 37±0.5°C using the USP type II dissolution apparatus. The samples were withdrawn at different time points. Aliquots of 5ml samples were withdrawn at regular intervals of time after filtration through 0.45µm pore size membrane filters, and analysis was carried out using UV spectrophotometer at 259.8 nm.

Comparison of In-vitro dissolution study of a prepared tablet with marketed formulation:

Here in-vitro dissolution study of a prepared tablet is compared with the marketed tablet formulation (INSTGRA Tablet).

Stability Study:

The stability study was carried out for optimized formulation as per the ICH guidelines. An accelerated stability study was performed at 40⁰C±2⁰C, 75%±5% RH with humidity and temperature control, were taken at 1, 2, 3 and 6 months. The tablets of the optimized formulation were HDPE (High-density polyethylene) bottle container and placed in a stability chamber. The samples were analyzed for physical appearance, disintegration time, drug content and drug release at regular interval.

RESULTS AND DISCUSSION:

SEDDS provides an opportunity for the improvement of the in vitro performance of poorly water-soluble drugs and thus serves as an ideal carrier for the delivery of drugs belonging to the Biopharmaceutics Classification System (BCS) classes II and IV. The current study was performed to define the role of self-emulsifying formulations to enhance the solubility and bioavailability of the antiretroviral drug Dolutegravir Sodium.

Solubility study:

The solubility of a drug in excipients plays an important role in determining the stability of the formulation, as many formulations undergo precipitation before undergoing in situ solubilization. Also to a successful formulation of Dolutegravir Sodium loaded SEDDS, the entire dose of Dolutegravir Sodium should be soluble in SEDDS ingredients. The solubility of Dolutegravir Sodium in various oils, surfactants, and co-surfactants is presented in (Table No. 2). Among various vehicles screened, Capmul MCM was selected as the oil phase showing the highest solubilization capacity Capmul MCM (18.50±0.04mg/ml). Tween 80 (14.05±1.18mg/ml) was used as surfactants, and PEG 400(18.26±0.26mg/ml) was chosen as Co-surfactant.

Table 2. Solubility of Dolutegravir Sodium in different oil.

Sr. No	Oil, Surfactant and cosurfactant	Solubility (mg/ml)
1	Castor oil	10.00± 0.50
2	Aniseed oil	15.00 ± 1.05
3	Oleic acid	5.00± 0.85
4	Capmul MCM	18.50 ± 0.40
5	Olive oil	2.00 ± 1.15
6	Isopropyl Myristate	10.00± 0.50
7	Tween 20	10.00± 0.10
8	Tween 80	14.05±1.18
9	Cremophore RH40	12.57± 0.21
10	PEG400	15.17± 0.31
11	Transcutol	12.22 ± 1.01
12	Propylene glycol	18.26 ± 0.26

Data are expressed as mean± SD (n=3)

Preliminary screening of surfactants for their emulsification ability:

It has been reported that well-formulated SEDDS is dispersed within seconds under gentle stirring conditions. The results showed that the highest % transmittance, i.e. highest emulsification efficiency, is acquired by Tween 20, followed by Tween 80> Cremophore RH 40 > Span 20. Tween 80 possessed the highest transmittance value and span 20 the lowest value.

Preliminary screening of co-surfactants:

The addition of a co-surfactant to the surfactant-containing formulation was reported to improve dispersibility and drug absorption from the formulation. In the present study, three co-surfactants, namely propylene glycol, polyethylene glycol 400, and Transcutol were compared. Capmul MCM as an oil and Tween 80 as surfactant showed good % transmittance with all the co-surfactant, transmittance 99.70% with Propylene glycol, > Transcutol 96.20%, > 91.60% with polyethylene glycol 400. In order to formulate SEDDS the components were selected based on Dolutegravir Sodium solubility in oily phases and surfactants. Tensile agents and cosurfactants have been screened to verify their capacity to emulsify the oily process. Based on the preliminary screening results, Capmul MCM was selected as an oily step, Tween 80 as a surfactant and Propylene glycol as a cosurfactant^11,12.

Construction of pseudo ternary phase diagram:

The pseudo ternary phase diagram of oil (Capmul MCM), surfactant (Tween80), Co-surfactant (Propylene glycol) were constructed (fig.1) with surfactant/co-surfactant ratio of 1:1, 1:2, 1:3. The shaded portion indicates the emulsification region. It was observed that the mixture with 20-40% oil and 60-80% surfactant mixture have shown higher transparency, better stability, and self-emulsification region.

Characterization Parameters of Optimize Dolutegravir Sodium-SEDDS Formulations

Table 3. Characterization Parameters of Optimize Dolutegravir Sodium-SEDD Formulations.

Formulations	% Transmittance ± S.D.	Self emulsification time (Sec.) ± S.D.	Globule size (nm) ± S.D.	PDI ± S.D.	Zeta potential (mV) ± S.D.	Drug Content (%) ± S.D.
F1	89.1± 0.35	30± 0.21	78.2±0.85	0.422±0.220	- 89.2±0.21	98.50± 0.50
F2	70.2± 0.57	45± 0.43	110.1±2.15	0.458±0.510	- 46.1±0.20	96.11± 0.20
F3	75.1±0.11	60± 0.83	180.2±0.40	0.545±2.110	- 35.2±0.11	94.08± 0.10
F4	68.9± 0.42	90± 0.45	172.1±1.05	0.522±0.260	- 29.1±0.25	91.10± 0.15
F5	99.0± 0.11	22± 0.14	57.7±0.36	0.409±0.460	- 69.6±0.34	99.10± 0.10
F6	69.1± 0.20	36± 0.63	115.1±1.15	0.470±1.780	- 42.5±0.77	97.41± 0.4
F7	74.1± 0.23	50±0.23	175.2±0.80	0.537±1.210	- 30.2±0.22	95.08± 0.15
F8	58.5± 0.54	60± 0.21	165.8±0.68	0.515±0.980	- 27.4±2.09	94.21± 0.20
F9	66.6± 0.42	95± 0.88	237.2±1.15	0.560±0.880	- 44.9±1.11	90.68± 0.10
F10	85.2± 0.31	35±0.19	88.2±1.01	0.445±0.190	- 85.2±0.71	97.23± 0.15
F11	59.1± 0.10	35± 0.91	245.1±1.19	0.570±2.100	- 40.2±1.28	96.10± 0.20
F12	75.2± 0.55	42± 0.51	112.1±0.97	0.463±0.330	- 38.1±0.21	97.01± 0.3
F13	62.4± 0.23	92± 0.54	260.2±1.82	0.585±0.170	- 35.4±0.27	90.31± 0.1
F14	59.8± 0.34	100± 0.94	310.6±2.51	0.598±2.010	- 22.1±0.21	88.51± 0.25
F15	55.6± 0.45	110± 0.13	325.2±2.35	0.610±0.720	- 18.8±0.74	88.18± 0.20

Data expressed as mean ± SD (n = 3)

Determination of self emulsification time:

The results of self emulsification time were shown in table no. 3. The lowest self emulsification time was observed for formulation F5 is 22 second.

Globule size determination:

The average globule size of F5 formulation was found to be 57.7 nm which was found to be minimum amongst all other formulations. The polydispersity index of F5 formulation was found to be 0.409.

Zeta potential determination:

The zeta potential of all SEDDS formulations with values ranging from -18.8 to -89.2mV, indicating a stable system and well-separated emulsion globules.

Optimization of S-SEDDS:

Two different adsorbents (Aerosil 200 and Neusilin US2) were used to convert liquid SEDDS into free flow powder. Among this Neusilin US2 adsorbent require only 80 mg to convert optimized liquid SEDDS into free flow powder whereas Aerosil 200 requires 100mg. All results were shown in Table 4. From the results, it was found that powder of Neusilin US2 adsorbent has excellent flow properties. Free flow powder of these two different adsorbents was filled into a capsule and an in-vitro dissolution test was performed. Neusilin US2 based free flow powder gives 61.50% drug release within 5 min and 88.50% drug release within 15 min which was faster drug release as compared to other adsorbent based on free flow granules of optimized liquid SEDDS. Results were shown in fig.3. From the above results, it was concluded that Neusilin US2 was a better adsorbent as compared to other adsorbent used in the study, so solid-state characterization was performed for Neusilin US2-based free flow powder by using DSC, PXRD & SEM.

Table 4: Adsorbent selection

Formulation

Adsorbent

Amount of

Liquid

SEDDS (ml)

Amount of adsorbent required to get free flow powder (mg)

Aerosil 200

0.2

100

Neusilin US2

0.2

The graphical representation of in-vitro drug release of Dolutegravir Sodium from free flow powder of 2 different adsorbents with standard errors is as shown below in Fig 2.

Fig. 2: In-vitro dissolution study of drug from two different adsorbents

DSC studies:

The DSC thermogram of pure drug Dolutegravir Sodium and solid SEDDS are as shown in Fig.3 (a) and (b). Pure drug substance shows a sharp endothermic peak at 355^°Cwhich shows the highly crystalline behavior of drug. There was no drug peak found in the solid SEDDS, indicating that the drug must be present in molecularly dissolved state in solid SEDDS.

Powder X-ray diffraction (XRD) analysis:

PXRD studies of Dolutegravir Sodium pure drug showed several sharp peak at 5-25^°θ. The solid SEDDS of optimized formulation (F5) revealed that sharp peak of mixture was observed at 15-25^°θ. The XRD patterns are shown in fig. 4 (a) and (b).

Fig. 4 (a): XRD spectra of pure drug

Fig. 4 (b): XRD spectra of optimized formulation (F5)

Evaluation of S-SEDDS tablets of Dolutegravir Sodium:

Tablet evaluation parameters of batch T1 to T9 were shown in table 5. All parameters were found to be satisfactory and within the specification for the Dolutegravir Sodium S-SEDDS tablet. The disintegration time for batch T5 was found to be 28 sec. This disintegration time was the lowest as compared to all other batches. In-vitro drug release was performed for the batch T1 to T9 and the results were shown in fig.5 (a) and (b) All batches show approximately 40.60% to 74.30% drug released within 15 minutes but among this batch, T5 shows 74.30 % drug released in 15 minutes which was faster as compared to other batches. So batch T5 was considered as an optimized batch and was used for further study.

Table 5: Evaluation parameters for S-SEDDS tablets of Dolutegravir Sodium

Factorial design used 3² for preparation of solid SEDDS
Formulation code	Hardness	Thickness	Uniformity of Weight	Friability	Disintegration time	Drug Content
	(kg/cm2)	(mm)	(mg)	(%)	(sec.)	(%)*
T1	4.00 ± 0.323	2.88 ± 0.168	150.2±1.200	0.06 ± 0.029	72 ± 2.517	98 ± 0.654
T2	3.96 ± 0.278	2.81 ± 0.188	149.5±1.500	0.19 ± 0.288	66 ± 4.041	97 ± 0.838
T3	4.03 ± 0.324	2.95 ± 0.184	149.8±1.100	0.39 ± 0.291	72 ± 2.517	98 ± 0.932
T4	3.90 ± 0.324	2.67 ± 0.084	150.2±1.200	0.08 ± 0.025	42 ± 2.517	98 ± 0.811
T5	3.63 ± 0.160	3.11 ± 0.119	148.8±1.800	0.04 ± 0.019	28 ± 2.000	99 ± 0.270
T6	3.96 ± 0.222	2.73 ± 0.168	149.5±1.300	0.08 ± 0.057	52 ± 2.517	97 ± 1.006
T7	4.01 ± 0.222	2.89 ± 0.125	150.5±1.100	0.12 ± 0.116	42 ± 2.517	98 ± 0.814
T8	3.95 ± 0.232	3.03 ± 0.47	148.8±1.600	0.07 ± 0.038	38 ± 2.887	98 ± 0.893
T9	4.04 ± 0.198	2.95 ±0.127	149.5±1.200	0.06 ± 0.041	45 ± 3.000	97 ± 0.966

Fig. 5 (a): In-vitro drug release profile of formulations T1 to T5

Fig. 5 (b): In-vitro drug release profile of formulations T6 to T9

Comparison of In-Vitro dissolution study of batch T5 with marketed formulation (INSTGRA Tablet)

In-vitro drug release study of batch T5 was compared with the marketed tablet formulation i.e. INSTGRA tablet (M). Marketed formulation shows just 62.30% drug release in 15 min whereas tablets of batch T5 shows 74.30 % drug release in the same time. Batch T5 shows 90.10% drug release in 30 min whereas marketed formulation shows 91.20% drug release in 45 min. which is shown in fig.6. This data clearly indicates that by formulating S-SEDDS which enhances solubility and release of drug was increased.

Fig. 6: In-vitro drug release comparison of T5 & marketed sample (M)

Accelerated stability studies:

Accelerated stability study (40°±2°C/75%±5% RH) was performed on optimized batch T5 for a period of 6 months. No significant changes were observed in appearance, disintegration time, globule size, zeta potential, drug content and drug release of the tablets. Results were shown in Table 6.

CONCLUSION:

In the present investigation, an S-SEDDS formulation was proposed to enhance the dissolution properties of a poor water soluble active ingredient Dolutegravir Sodium. The optimized liquid SEDDS (F5) was transformed into S-SEDDS by using Neusilin US2 as the inert solid carrier. The drug release studies revealed a higher and uniform release of Dolutegravir Sodium from the formulations. The solid-state characterization of S-SEDDS by using DSC, PXRD and SEM studies indicated that there is no specific physicochemical interaction between pure drug and drug-loaded S-SEDDS. The disintegration time of the optimized T5 batch was found to be 28 sec and 90.10% drug release in 30 min. In-vitro drug release of the T5 was highly significant as compared to a marketed conventional tablet (M). The optimized S-SEDDS tablet (T5) was found to be chemically and physically stable for 6 months. Thus it can be concluded that S-SEDDS Dolutegravir Sodium would be a promising dosage form to treat human immunodeficiency virus (HIV) in treatment of Pediatric and Geriatric patients.

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Received on 08.08.2021 Modified on 10.10.2021

Research J. Pharm. and Tech 2022; 15(9):4158-4165.

DOI: 10.52711/0974-360X.2022.00698

Time	Parameters
(In Months)	Disintegration time (sec.)	Drug content (%)	Drug release (%)	Globule Size	Zeta Potential
1 M	26±1.520	99.50±0.720	99.10±0.660	56.7±0.20	0.407±0.460
2 M	27±1.150	97.50±0.500	98.50±0.590	58.7±0.12	0.422±0.220
3 M	26±1.000	98.10±1.500	98.30±0.480	55.7±0.40	0.412±0.325
6 M	28±0.570	96.80±0.800	97.50±0.140	57.7±0.30	0.405±0.210