Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery

 

Kumara Swamy S1*, Ramesh Alli2

1Asst. Professor, Department of Pharmaceutics, Vaagdevi Pharmacy College,

Bollikunta, Warangal, Telangana State, India.

2Department of Pharmaceutics, Vaagdevi Pharmacy College, Bollikunta, Warangal, Telangana State, India.

*Corresponding Author E-mail: kumar4koti@gmail.com, rameshalli567@gmail.com

 

ABSTRACT:

The purpose of this study was to develop and evaluate irbesartan (IS) loaded solid lipid nanoparticles (SLNs; IS-SLNs) that might enhance the oral bioavailability of IS. IS, an angiotensin-receptor antagonist, used to treat hypertension. However, poor aqueous solubility and poor oral bioavailability has limited therapeutic applications of IS. Components of the SLNs include either of trimyristin/tripalmitin/tristearin/trilaurate/stearic acid/beeswax, and surfactants (Poloxamer 188 and soylecithin). The IS-SLNs were prepared by hot homogenization followed by ultrasonication method and evaluated for particle size, poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro drug release. The physical stability of optimized formulation was studied at refrigerated and room temperature for two months. The optimized IS-SLN formulation (F4) had a mean diameter of about 217.6±3.62 nm, PDI of 0.163±0.032, ZP of -28.5±4.12, assay of 99.8±0.51 and EE of 93.68±2.47%. The formulation showed sustained drug release compared with control formulation over 24 h. Optimized formulation was found to be stable over two months. IS-SLN showed nearly spherical in shape using and converted to amorphous form by DSC. Thus, the results conclusively demonstrated SLNs could be considered as an alternative delivery system for the oral bioavailability enhancement of IS.

 

KEYWORDS: Irbesartan, solid lipid nanoparticles, particle size, in vitro release, SEM, DSC.

 

 


INTRODUCTION:

The oral bioavailability of poorly water-soluble drugs and drugs prone for first-pass metabolism often exhibit low bioavailability as their absorption could be kinetically-limited by low rates of dissolution and capacity-limited by poor solubility, when these were administered in traditional solid formulations1.

 

Problems such as poor solubility or chemical stability in the environment of the gastrointestinal tract, poor permeability through the biological membranes or sensitivity to metabolism are well known to result in the rejection of potential drug candidates as practical products2,3. Various approaches have been used to enhance the oral bioavailability of poorly soluble drugs. These approaches includes; enhance the solubility and dissolution rate using solid dispersion by complexation4-6, liquisolid compacts7, by avoiding the pre-systemic metabolism using buccal delivery8-11, semi solid dispersions12, prolong the drug release using floating delivery13-15, sustained delivery16,17, multiunit dosage form18; reducing the particle size by using micronization and nanonization such as self-emulsifying delivery19, solid lipid nanoparticles20, cubosmes21, nanosuspension22, transfersomes23,24, nanocrystals25,  microemulsion26 and nanoemulsion27.

 

The use of lipid-based drug delivery systems like solid lipid nanoparticles (SLNs) has generated much academic and commercial interest as a potential formulation strategy for improving the oral bioavailability to overcome the hepatic first-pass metabolism and to enhance the oral bioavailability. These systems enhance the lymphatic transport of the lipophilic drugs and therefore increase the bioavailability28. Lot of information is available in literature showing the improvement in oral bioavailability by SLNs. It is known that colloidal drug delivery systems alter the pharmacokinetic parameters of a drug. Among various approaches, lipid nanocarriers (solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs)) considered to be as vehicle for one of the novel delivery system for improvement of oral bioavailability29-32.

 

SLNs are sub-micron colloidal carriers having a size range of 50–1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. SLNs were developed in the last decade as an alternative system to the existing traditional carriers, i.e. emulsions, liposomes and polymeric nanoparticles33,34.  These are related to emulsions, where the liquid lipid, oil is substituted by a solid lipid. SLNs offer unique properties such as small size, large surface area and high drug loading and are attractive for their potential to improve performance of active pharmaceutical ingredients. The advantages of SLNs include drug targeting, biocompatibility, nontoxicity, drug release modulation and small scale production35.

 

Irbesartan is a non-peptide angiotensin II type 1 (AT1) receptor antagonist, used in the treatment of hypertension and heart failure36. The major drawback in the therapeutic application and efficacy of irbesartan as an oral dosage form is its very low aqueous solubility and first-pass metabolism37, 38. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, SLNs can be used. These systems enhance the lymphatic transport and increase the bioavailability. In view of this, it becomes a good candidate for the development of SLN drug delivery system.

 

The aim of the current investigation was to prepare and characterize the IS-SLNs by hot homogenization followed by ultrasonication method. Prepared IS-SLNs evaluated for particle size, zeta potential and poly dispersity index (PDI) using zeta sizer; determining the total drug content and entrapment efficiency using UV visible spectrophotometer. The surface morphology of IS-SLNs by Scanning Electron Microscopy. In vitro drug release studies of the prepared SLN formulations by dialysis method. Further, stability studies of the optimized IS-SLN formulation at both room temperature and refrigerated temperature for two months.

 

Preparation of irbesartan loaded solid lipid nanoparticles suspension:

Irbesartan loaded SLNs were prepared by hot homogenization followed by the ultra sonication39-41. IS, lipid, and soya lecithin were dissolved in 5mL of 1:1 mixture of chloroform and methanol. Organic solvents were completely removed using a rota evaporator (Heidolph, Schwabach, Germany). The drug embedded lipid layer was molten by heating to 5°C above melting point of the lipid. Aqueous phase was prepared by dissolving Poloxamer 188 in double distilled water and heated to same temperature (based on lipid melting point) of oil phase. Hot aqueous phase was added to the oil phase, and homogenization was carried out (at 10000-12000rpm) using homogenizer (Diax900, Heidolph, Germany) for 5-10 min. The coarse hot oil in water emulsion so obtained was ultrasonicated using a 12T probe sonicator (Vibracell, Sonics, CT, USA) for 40-60 min. Irbesartan loaded solid lipid nanoparticles were obtained by allowing hot nanoemulsion to cool to room temperature. The composition of various formulations is shown in Table 1.


 

Table 1: Composition of irbesartan loaded solid lipid nanoparticles

Formulation ingredient

Formulation code

F 1

F2

F3

F 4

F 5

F 6

F 7

F 8

ORGANIC PHASE

Irbesartan (mg)

10

10

10

10

10

10

10

10

Dynasan-112 (mg)

200

-

-

-

400

-

-

-

Dyanaasn-116 (mg)

-

200

-

-

-

400

-

-

Dyanasan-118 (mg)

-

-

200

-

-

-

400

-

Dyanasan-114 (mg)

-

-

-

200

-

-

-

400

Soya lecithin

200

200

200

250

200

200

200

250

Chloroform: methanol (mL) - 1:1

8

8

8

8

8

8

8

8

AQUEOUS PHASE

Polaxomer 188

200

200

200

300

200

200

200

300

Double distilled water (mL)

10

10

10

10

10

10

10

10

 


Preparation of IS suspension (IS-CS):

About 50mg of sodium carboxy methyl cellulose was taken in a mortar and triturated for 3min then 10mg of irbesartan was added to it and triturated for 3 min. To it, 10mL of water was added and again triturated for 5 min to form IS-CS.

 

EVALUATION OF THE DEVELOPED FORMULATION:

Measurement of Particle Size, Poly dispersity index (PDI) and Zeta Potential of IS-SLNs:

The size, PDI and zeta potential of IS-SLNs were measured using a Malvern Zetasizer (Nano ZS90). The prepared SLN of 100µL was diluted to 5mL with double distilled water to get optimum Kilo Counts Per Second (KCPS) of 50-200 for measurements42.

 

Determination of entrapment efficiency:

Entrapment efficiency (EE) was determined by measuring the concentration of free drug (unentrapped) in aqueous medium as reported previously43. The aqueous medium was separated by ultra-filtration using centrisart tubes (Sartorius, Goettingen, Germany), which consisted of filter membrane (M.Wt. cut off 20000Da) at the base of the sample recovery chamber. About 2.5mL of the formulation was placed in the outer chamber and sample recovery chamber was placed on top of the sample and centrifuged. The SLN along with encapsulated drug remained in the outer chamber and aqueous phase moved into the sample recovery chamber through filter membrane. The amount of irbesartan in the aqueous phase was estimated by UV visible spectrophotometer44,45.

 

Determination of total drug content:

About 100mL of the SLN formulation was dissolved in chloroform and methanol mixture (1:1) and then further dilutions were made with organic solvent46,47. The amount of IS in formulations was calculated by UV visible spectrophotometry.

 

In vitro drug release studies:

In vitro release studies were performed using dialysis bag method. Dialysis membrane having pore size 2.4 nm and molecular weight cut-off between 12,000 -14,000 was used for the release studies48. Dialysis membrane was soaked overnight in double distilled water prior to the release studies. Phosphate buffer pH 6.8 was used as release media. The experimental unit consists of a donor and receptor compartment. Donor compartment consists of a boiling tube which was cut open at one end and tied with dialysis membrane at the other end into which SLN dispersion of 2mL was taken for release study. Receptor compartment consists of a 250mL beaker which was filled with 100mL release medium and the temperature of it was maintained at 37±0.5°C. At 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24-hour time points, 5mL samples were withdrawn from receiver compartment and replenished with the same volume of release medium. The collected samples were suitably diluted and analyzed by UV-Visible spectrophotometer.

 

Physical Stability Studies:

IS-solid lipid nanoparticles were stored at room and refrigerated temperature for 60 days, and average size, zeta potential and poly dispersity index were determined49-51. The number of samples estimated was in triplicate.

 

Lyophilization of SLNs:  

The optimized SLNs containing 10% w/v maltose for IB-SLNs and kept in deep freezer at -40°C (Sanyo, Japan) for overnight. The frozen samples were then transferred into freeze-dryer (Lyodel, Delvac Pumps Pvt. Ltd, India). Vacuum was applied and sample was subjected to various drying phases for about 48hrs to get powdered lyophilized product52.

 

Drug excipients compatibility study by differential scanning calorimetry (DSC):

Irbesartan, pure lipids, physical mixture of drug and lipid and optimized SLN formulation was subjected to DSC analysis. It quantifies the enthalpy changes during endothermic or exothermic effects. The instrument was calibrated with indium (calibration standard, purity > 99.99%) for melting point and heat of fusion. About 8 mg of sample was taken for analysis into standard aluminium pans. An empty pan was used as reference. The heating rate was increased at the rate of 10°C/min and the obtained thermograms were observed for any type of interaction53,54.

 

Morphology of SLNs by Scanning electron microscopy (SEM):

The morphology of solid lipid nanoparticles was studied by Scanning Electron Microscope (SEM, Hitachi, Japan) at Osmania university, Hyderabad. Freeze dried solid lipid nanoparticles of CC/ND/RC were diluted with double distilled water (1 in 100) and a drop of SLN formulation was placed on sample holder and air dried. Then, the sample was observed at accelerating voltage of 15000 volts at various magnifications. Imaging was carried out in high vacuum55.

 

RESULTS AND DISCUSSION:

Characterization of prepared Irbesartan solid lipid nanoparticles:

Particle Size, ZP and PDI of prepared IS-SLNs:

All the prepared samples were analyzed in order to determine their particle size distribution, zeta potential and PDI values. The results are represented in Table 2.  Formulation containing Dynasan 112 (F1 and F5) showed particle size 300.7±0.86nm and 344±3.35nm, PDI 0.290 and 0.28, zeta potential -24.5±4.12 mV and -19.10±5.12, respectively. Formulations containing Dynasan 116 (F2 and F6) showed particle size ranging from 379.9±1.72 and 342±2.92 nm, PDI 0.288±0.012 and 0.297±0.084 and ZP of -22.6±3.40 and -21.8±3.23 mV, respectively. Formulations containing Dynasan 118 (F3 and F7) showed particle size ranging from 339.2 ±1.85 and 318±2.40nm, PDI 0.297±0.007 and 0.236±0.08 and ZP of -24.4±4.80 and -26.0±3.81mV, respectively. The ZP of all the formulations within the range of ±20 mV and considered to be stable56. Poloxamer 188 was used in the formulation as surfactant. It is a non-ionic surfactant and decreased the electrostatic repulsion between the particles following sterical stabilization of the nanoparticles by forming a coat around their surface for maintaining the stability of SLN57. From the results obtained, formulations containing Dynasan 114 showed better size, PDI and good zeta potential when compared to other formulations.

 

Table 2:  Particle Size, zeta potential and PDI of IS-SLN formulations (mean±SD, n=3)

Formulation

Size (nm)

PDI

ZP (mV)

F1

300.7±0.86

0.290±0.016

-24.5±4.12

F2

379.9 ± 1.72

0.288±0.012

-22.6±3.40

F3

339.2 ±1.85

0.297±0.007

-24.4±4.80

F4

217.6±3.62

0.163±0.032

-28.5±4.12

F5

344 ± 3.35

0.228±0.031

-19.10±5.12

F6

342 ± 2.92

0.297±0.084

-21.8±3.23

F7

318 ±  2.40

0.236±0.08

-26.0±3.81

F8

325.4 ± 2.02

0.212±0.05

-25.1±5.12

 

Determination of EE and total drug content:

All the formulations were analyzed for EE and total drug content. Results are tabulated and represented in Table 3. EE of IS-SLNs ranged from 72.26±3.51 to 93.68±2.47% and drug content of 97.8±1.63 to 99.8±0.51%, respectively. Formulations containing Dynasan-114 (F4 and F8) showed total drug content ranging 99.8±0.51 and 99.4±2.51% and entrapment efficiency 93.68±2.47% and 90.23±2.93%, respectively.

 

Table 3:  Entrapment efficiency and assay of IS-SLN formulations (mean±SD, n=3)

Formulation

EE (%)

Assay (%)

F1

89.12±2.84

99.2±1.08

F2

86.92±2.65

98.4±0.84

F3

90.61±4.31

98.7±2.06

F4

93.68±2.47

99.8±0.51

F5

72.26±3.51

99.1±0.39

F6

78.39±2.68

98.7±0.92

F7

88.41±4.31

97.8±1.63

F8

90.23±2.93

99.4±2.51

 

From the results obtained all formulations showed good entrapment efficiency (as represented in Table 3) and formulation Dynasan 114 (F4) showed higher values compared to Dynasan 116, Dynasan 118 and Dynasan 112. This might be because of the long-chain fatty acids attached to the glyceride resulting in increased accommodation of lipophilic drugs58,59 (Among all IS-SLN preparations formulation (F4) with lipid (Dyanasan-114): soylecithin ratio of (1:1.5) showed higher values compared to other formulations.

 

In vitro drug release studies of irbesartan-SLN and suspension by dialysis method:

In vitro release of irbesartan from IS-SLNs was studied in pH 6.8 phosphate buffer by dialysis method. In pH 6.8 phosphate buffer, the cumulative % of release from formulations F1-F8 was 66.26%, 72.09%, 74.24%, 77.05%, 80.45%, 85.47%, 86.07% and 90.03%, respectively in 24 hours. The release profiles of SLN formulations exhibited a typical biphasic pattern with an initial rapid phase followed by a slow phase in phosphate buffer (Figure 1 and 2).

 

Formulation F4 showed maximum release of 90.03% in pH 6.8 phosphate buffer during 24 hours. In comparison, F4 formulation exhibited reasonably good particle size, better PDI, high zeta potential value, and the higher entrapment efficiency with release of drug from the lipid matrix in pH 6.8 phosphate buffer, hence it was considered as the optimized formulation.

 

 

Figure 1: In vitro release of IS from IS-SLNs (F1-F4 and IC-CS) in pH 6.8 phosphate buffer (mean±SD, n=3)

 

Formulations containing Dynasan 112, Dynasan 116, Dynasan 118, and Dynasan 114 showed drug release ranging from 85.47% to 66.26%, 80.45% to 74.24%, 86.07% to 72.09% and 90.3% to 77.05% respectively in 6.8 pH buffer as represented in Table 4.12. Due to increased lipid content, the release was significantly retarded in all the prepared SLNs when compared in each set. F4 formulation showed highest cumulative release among all the prepared SLNs. All the experiments were carried out in triplicate. Further, all the formulations showed prolonged release compared with control formulation.

 

Figure 2: In vitro release of IS from IS-SLNs (F1-F4 and IC-CS) in pH 6.8 phosphate buffer (mean±SD, n=3)

 

Stability study of optimized SLN (F4):

The stability of the optimized SLN formulation (F4) was ascertained by monitoring the physical appearance, particle size, PDI, ZP of irbesartan after storage at refrigerated and room temperature for a period of two months. Results are shown in Table 4. No drastic changes in particle size, PDI and ZP were observed when stored at refrigerated temperature for a period of 3 months. But, PDI was changed when stored at 25oC, while other parameters remained same. However, relatively less change in size was noticed in samples stored at refrigerated temperature were observed. This could be due to the stable nature of lipid matrix formed during IB-SLNs preparation.


 

Table 4: Effect of storage at refrigerated and room temperature on size, PDI, zeta potential of optimized (FC4) SLN formulation (mean±SD, n = 3)

Day

At room temperature

At refrigerated temperature

Size (nm)

PDI

ZP (mV)

Size (nm)

PDI

ZP (mV)

1

218.8±1.85

0.186±0.025

-28.2±2.74

217.8±2.03

0.198±0.022

-26.28±1.74

30

225.5±2.14

0.225±0.05

-25.0±2.05

232.7±2.84

0.258±0.018

-24.32±1.88

60

236.6±1.89

0.234±0.06

-24.9±2.87

242.5±1.76

0.273±0.065

-24.21±2.54

 


Lyophilization of optimized IS-SLN:

The optimized (F4) SLN formulation was freeze dried with 10% maltose and resulted in SLN powder. Upon reconstitution, increase in size, PDI and zeta potential were noticed (Table 5). Due to removal of water in freeze drying process, particle attractive forces would increase59-61, this might be reason for increase in the particle size of the SLN formulation.

 

Table 5: Effect of lyophilization on size, PDI, zeta potential of optimized (F4) IS-SLN formulation (mean±SD, n = 3)

Parameter

Pre-lyo

Post-lyo

Size (nm)

223.6±2.4

465.7±10.5

PDI

0.216±0.03

0.433±0.06

ZP (mV)

-28.9±2.74

-26.5±1.32

 

Drug-excipient compatibility studies by DSC:

The compatibility status of the lipids in the SLN formulation was investigated by DSC and was based on the fact that different lipids possessed different melting points and enthalpies. DSC thermograms of pure drug, lipids, physical mixtures and lyophilized SLN formulation are showed in Figure 3.

 

The DSC thermogram of pure CC showed a sharp endothermic peak at 175.80°C with high enthalpy and Dyanasan-114 showed a sharp endothermic peak at 78.98°C. Physical mixture of drug and Dyanasan-114 showed sharp endothermic peaks at 181.53°C and 78.98°C, respectively, however with less enthalpy.


 

Figure 3: DSC thermograms of A) pure IS, B) pure lipid, C) physical mixture of drug and lipid, D) lyophilized IS-SLN formulation


 

In this case, melting endotherm of drug was well preserved with slight changes in terms of broadening or shifting in the temperature of the melt. It is known that the quantity of material used, especially in drug-excipient mixtures, could influence the peak shape and enthalpy. Thus, these minor changes in the melting endotherm of drug could be due to the mixing of drug and excipient, which lowered the purity of each component in the mixture and this, might not necessarily indicate potential incompatibility62,63. The absence of endotherm peak of drug in lyophilized SLN formulation (F4) unravels the conversion of native crystalline state of the drug to amorphous state.

 

Morphology of SLN using Scanning electron microscopic study:

Optimized SLN formulation (F4) was studied for surface morphology a using SEM. The particles possessed smooth surface and have spherical shape, but with increased particle size due to lyophilization process64. The agglomeration phenomenon increased the size as shown in Figure 4.

 

Figure 4: SEM image of lyophilized optimized IS-SLN formulation

 

CONCLUSIONS:

Irbesaratn loaded solid lipid nanoparticles were successfully prepared by using hot homogenization and ultra sonication method. The prepared SLNs showed spherical in shape with nano particle size and homogenous distribution. DSC revealed that no interaction and also conversion of IS onto amorphous form. IS-SLNs showed prolonged drug release compared with control suspension formulation. The optimized formulation stable for two months under storage testing conditions. Hence, we can conclude that solid lipid nanoparticles provide controlled release of the drug and these systems are used as drug carriers for lipophilic drugs, to enhance the bioavailability of poorly water-soluble drugs through nanoparticles, as a drug delivery system.

 

DECLARATION OF INTEREST:

The authors declare that no conflict of interest.

 

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35.    Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002 54 Suppl 1:S 131-55.

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38.    Kamisetti RR, Vinitha Brungi, S. Bennuru, Sr. Cheeli, RM. Gupta Vankadari. Studies on the development of Orally Disintegrating Tablets of Irbesartan. Asian J Pharm Res. 2020; 10(1): 01-07.

39.    Narendar D, Kishan V. Pharmacokinetic and pharmacodynamic studies of nisoldipine-loaded solid lipid nanoparticles developed by central composite design. Drug Dev Ind Pharm. 2015; 41 (12), 1968-77.

40.    Thulasi Ram D, Subhashis Debnath, M. Niranjan Babu, T. Chakradhar Nath, Thejeswi B. A Review on solid Lipid Nanoparticles. Research J Pharm and Tech. 2012; 5(11): 1359-1368.

41.    Usha G, Narendar D, Kishan V. Preparation, characterization and in vivo evaluation of felodipine solid lipid nanoparticles to improve the oral bioavailability. Int J Pharma Sci Nanotech. 2015; 8 (4), 2995-3002.

42.    Arun B, Narendar D, Kishan V. Development of olmesartan medoxomil lipid-based nanoparticles and nanosuspension: preparation, characterization and comparative pharmacokinetic evaluation. Artificial cells, nanomed and biotech. 2018; 46(1), 126-137.

43.    Narendar D, Kishan V. Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation. Drug Deli. 2016; 23 (2), 395-404.

44.    Nalini CN, Mathivanan N. A review on analytical methods of irbesartan and its combinations in pharmaceutical dosage forms. Current Pharmaceutical Analysis. 2020 Dec 1; 16(8): 1020-9.

45.    Vishal VB, Indrajeet S. Patil, Omkar A. Patil, Srinivas K. Mohite. UV spectroscopy analysis and degradation study of irbesartan. Asian J Pharm Ana. 2018; 8(2): 69-72.

46.    Gorre TR, Swetha E, Narendar D. Role of isradipine loaded solid lipid nanoparticles in the pharmacodynamic effect of isradipine in rats. Drug res. 2017; 67(03): 163-169.

47.    Rohan RV, Swati S. Talokar, V. R. Salunkhe, C. S. Magdum. formulation development and optimization of simvastatin loaded solid lipid nanoparticles. Asian J Res Pharm Sci. 2017; 7(1): 49-52.

48.    Dudhipala N, Ahmed AA. Amelioration of ketoconazole in lipid nanoparticles for enhanced antifungal activity and bioavailability through oral administration for management of fungal infections. Chemistry and Physics of Lipids. 2020; 232: 104953.

49.    Ashok P, Meyyanathan SN, Jawahar N, Vadivelan R. Irbesartan formulation and evaluation of loaded solid lipid nanoparticles by microemulsion technique. Asian J Pharm Tech. 2020; 10(4): 228-230.

50.    Suvarna G, Narender D, Kishan V. Preparation, characterization and in vivo evaluation of rosuvastatin calcium loaded solid lipid nanoparticles. Int J Pharm Sci Nanotech. 2015; 9: 2779-85.

51.    Dudhipala N, Janga KY, Gorre T. Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation. Artificial cells, nanomedicine, and biotechnology. 2018 Nov 5; 46(sup2): 616-25.

52.    Dudhipala N, Puchchakayala G. Capecitabine lipid nanoparticles for anti-colon cancer activity in 1,2-dimethylhydrazine-induced colon cancer: preparation, cytotoxic, pharmacokinetic, and pathological evaluation. Drug Dev Ind Pharm. 2018; 44: 1572–1582.

53.    Dinesh S, Pratibha S, Pandey KN, Vishal V, Vijay K, Saxena AK. Thermal and morphological behavior of PEEK/PEI blends with polyphosphazene coated carbon nanotube. Asian J Research Chem. 2012; 5(5): 650-654.

54.    Dudhipala N, Ahmed AAY, Nagaraj B. Colloidal lipid nanodispersion enriched hydrogel of antifungal agent for management of fungal infections: comparative in-vitro, ex-vivo and in-vivo evaluation for oral and topical application. Chemistry and Physics of Lipids. 2020: 104981.

55.    Narendar D, Karthik yadav J. Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: Optimization, in vitro and in vivo evaluation. Drug Dev Ind Pharm. 2017; 43(7): 1205-1214.

56.    Youssef A, Dudhipala N, Majumdar S. Ciprofloxacin loaded nanostructured lipid carriers incorporated into in-situ gels to improve management of bacterial endophthalmitis. Pharmaceutics. 2020; 12: 572.

57.    Narendar D, Thirupathi G. Neuroprotective effect of ropinirole loaded lipid nanoparticles hydrogel for Parkinson’s disease: preparation, in vitro, ex vivo, pharmacokinetic and pharmacodynamic evaluation. Pharmaceutics, 2020, 12(5): 448.

58.    Nachammai K, Keerthi G S Nair, Ramaiyan Velmurugan, Sathesh Kumar S Pavithra K. Sustained – release study on mefenamic acid and mosapride loaded solid lipid nanoparticles: in vitro characterization. Research J Pharm and Tech. 2020; 13(11): 5391-5395.

59.    Dudhipala N, Veerabrahma K. Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: Pharmacokinetic and pharmacodynamic evaluation. European Journal of Pharmaceutics and Biopharmaceutics. 2017 Jan 1; 110: 47-57.

60.    Ramanuj Prasad Samal, Pratap Kumar Sahu. Formulation development and in vitro characterization of solid lipid nanoparticles of felbamate. Research J Pharm and Tech. 2020; 13(9): 4185-4189.

61.    Butreddy A, Dudhipala N, Janga KY, Gaddam RP. Lyophilization of small-molecule injectables: an industry perspective on formulation development, process optimization, scale-up challenges, and drug product quality attributes. AAPS PharmSciTech. 2020 Oct; 21(7): 1-20.

62.    Kishan V, Sandeep V, Narendar D, Arjun N. Lacidipine loaded solid lipid nanoparticles for oral delivery: preparation, characterization and in vivo evaluation. International Journal of Pharmaceutical Sciences and Nanotechnology. 2016 Nov 30; 9(6): 3524-30.

63.    Narendar D, Arjun N, Someshwar K, Rao YM. Quality by design approach for development and optimization of quetiapine fumarate effervescent floating matrix tablets for improved oral bioavailability. Journal of Pharmaceutical Investigation. 2016 Jun 1; 46(3): 253-63.

64.    Janga KY, Tatke A, Dudhipala N, Balguri SP, Ibrahim MM, Maria DN, Jablonski MM, Majumdar S. Gellan gum-based sol-to-gel transforming system of natamycin transfersomes improves topical ocular delivery. Journal of Pharmacology and Experimental Therapeutics. 2019 Sep 1; 370(3): 814-22.

 

 

 

Received on 19.11.2020            Modified on 25.01.2021           

Accepted on 11.03.2021   ©Asian Pharma Press All Right Reserved

Asian Journal of Pharmacy and Technology. 2021; 11(2):97-104.

DOI: 10.52711/2231-5713.2021.00016