Self-nanoemulsifying Drug Delivery Research Articles

Lipid Horizons: Recent Advances and Future Prospects in LBDDS for Oral Administration of Antihypertensive Agents.

The lipid-based drug delivery system (LBDDS) is a well-established technique that is anticipated to bring about comprehensive transformations in the pharmaceutical field, impacting the management and administration of drugs, as well as treatment and diagnosis. Various LBDDSs verified to be an efficacious mechanism for monitoring hypertension systems are SEDDS (self-nano emulsifying drug delivery), nanoemulsion, microemulsions, vesicular systems (transferosomes and liposomes), and solid lipid nanoparticles. LBDDSs overcome the shortcomings that are associated with antihypertensive agents because around fifty percent of the antihypertensive agents experience a few drawbacks including short half-life because of hepatic first-pass metabolism, poor aqueous solubility, low permeation rate, and undesirable side effects. This review emphasizes antihypertensive agents that were encapsulated into the lipid carrier to improve their poor oral bioavailability. Incorporating cutting-edge technologies such as nanotechnology and targeted drug delivery, LBDDS holds promise in addressing the multifactorial nature of hypertension. By fine-tuning drug release profiles and enhancing drug uptake at specific sites, LBDDS can potentially target renin-angiotensin-aldosterone system components, sympathetic nervous system pathways, and endothelial dysfunction, all of which play crucial roles in hypertension pathophysiology. The future of hypertension management using LBDDS is promising, with ongoing reviews focusing on precision medicine approaches, improved biocompatibility, and reduced toxicity. As we delve deeper into understanding the intricate mechanisms underlying hypertension, LBDDS offers a pathway to develop next-generation antihypertensive therapies that are safer, more effective, and tailored to individual patient needs.

Optimization and Validation of Sensitive UPLC-PDA Method for Simultaneous Determination of Thymoquinone and Glibenclamide in SNEDDs Formulations Using Response Surface Methodology

The development of analytical procedures capable of simultaneous determination of two or more drugs is in crucial demand due to the availability of different formulations that are composed of different APIs. The presented study aimed to optimize and validate a simple, accurate, and sensitive UPLC analytical method for the simultaneous determination of thymoquinone (TQ) and Glibenclamide (GB) using response surface methodology, and apply this method in pharmaceutical formulations. A 32 full design of experiment was utilized to study the impacts of the independent parameters (acetonitrile ACN concentration, A; and column temperature, B) on the drugs’ analytical attributes (viz, retention time, peak area, and peak asymmetry, in addition to the resolution between TQ and GB peaks). The results revealed that the independent parameters exhibited highly significant (p < 0.05) antagonistic effects on retention times for TQ and GB peaks, in addition to the agnostic effect on GB peak symmetry (p-value = 0.001). Moreover, antagonistic impacts (p < 0.05) on the resolution between TQ and GB peaks were found for both independent factors (A and B). The statistical software suggested 46.86% of ACN (A) and 38.80 °C for column temperature (B) for optimum analytical responses. The optimized green method was discovered to be acceptable in terms of selectivity, precision, accuracy, robustness, sensitivity, and specificity. Moreover, the optimized simultaneous method was successfully able to determine the contents of TQ and GB in self-nanoemulsifying drug delivery (SNEDD) formulation, in which the results showed that GB and TQ content within the prepared formulations were 1.54 ± 0.023 and 3.62 ± 0.031 mg/gm, respectively. In conclusion, the developed assay was efficient and valid in analyzing TQ and GB simultaneously in bulk and self-nanoemulsifying drug delivery system (SNEDDs) formulations.

Formulation and evaluation of self-nanoemulsifying drug delivery system for improved oral delivery of exemestane hydrochloride

Exemestane HCl (EXM) is a new irreversible steroidal aromatase inhibitor for adjuvant therapy of hormonally sensitive breast cancer in post-menopausal women. EXM's low water solubility hinders solid oral dosage form development. The current work aims to increase EXM solubility by formulating the self nanoemulsifying drug delivery (SNEDDs) system. The water titration approach was employed in the development of SNEDDs. Based on solubility tests, SNEDDs components Caprol Microexpress and Labrafac were selected as oil phase, Tween 80 as surfactant, and Triacetin as co-surfactant. Phase investigations were carried out with various surfactant:co-surfactant ratios (1:1, 1:2, 1:3, 2:1, 3:1). Tween 80: triacetin (1:2) and (1:3) with Caprol Microexpress and Labrafac alone had the greatest nanoemulsion area. Visual evaluation, optical clarity, particle size, medication concentration, and viscosity were used to optimise 10 formulations. F3, F7, and F8 batches had the lowest size at 7.313 ± 1.44 nm, 6.379 ± 0.45 nm, and 14.67 ± 0.37 nm, respectively, with self-emulsification times under 1 min.But optical clarity data was suggested that F7 was not showing any precipitation up to 24 H. Overall, the developed SNEDDS formulation could be a promising approach for the improved oral delivery of EXE with enhanced dissolution and bioavailability.

Self-Solidifying and Self-Nanoemulsifying Drug Delivery System of Itraconazole

Objective: To improve solubility, dissolution, and permeability of BCS class II drug Itraconazole (ITZ) using a self solidifying self nano emulsifying drug delivery system (SNEDDS). Method: The solubility of ITZ was assessed in oils, surfactants, co-surfactants, and buffers. Surfactants, co-surfactants, and combination of surfactants (S-comb) were selected on the basis of emulsification efficacy test. The ability to solidify self emulsifying mixture was assessed and solid SNEDDSS was developed and optimised. Finding: Solubility of ITZ was found maximum in 0.1N HCl (0.120  0.07mg/mL) followed by SGF (0.089  0.01mg/mL). Out of 20 oils screened, Peceol showed highest solubility. Among all surfactants and co-surfactants studied, Labrafil M 1944 CS (LM 1944) showed highest potential to solubilize ITZ (14.91 mg/g). The globule size of the optimised formulation was found to be 40.11 nm with PDI of 0.144. Zeta potential study revealed the stability of the SNEDDS. Drug content of solid SNEDDS of ITZ was found within the range of 98.11% to 102.51%, which was found in the acceptable limit. It was observed that ITZ solid SNEDDS (SSNEDDS) showed a promising improvement in the in vitro dissolution profile compared to the plain ITZ and marketed product in all three-dissolution media. Nearly 3-fold enhancement of permeability of ITZ was attributed by uniformly dispersed globules with nano size. Analytical characterization demonstrated that the drug and excipients are compatible with amorphous characteristics of the ITZ. Novelty: The developed self solidifying SNEDDS of ITZ showed enhanced solubility, dissolution, and permeability in comparison to the pure drugs (ITZ). Self solidifying SNEDDS would be a novel approach to overcome the limitations associated with liquid dosage forms. Keywords: Itraconazole; Solubility; Bioavailability; Self Nano Emulsifying Drug Delivery System (SNEDDS); Permeability

In-Vivo Pharmacokinetics Study of Exemestane Hydrochloride Self-nanoemulsifying Drug Delivery Systems via Oral Route

Exemestane HCl (EXM) is a novel irreversible steroidal aromatase inhibitor for the adjuvant treatment of hormonally responsive breast cancer in postmenopausal women. Poor aqueous solubility of EXM is the biggest hurdle for developing solid oral dosage forms. That’s why the current study aims to evaluate the pharmacokinetics of formulating the EXM loaded self nano emulsifying drug delivery (SNEDDs) system. SNEDDs were formulated using Labrafac CC (20% w/v), Tween 80 (27%w/v), and Triacetin (54%w/v) as oil, surfactant, and co-surfactant, respectively, by water titration method. A comparative Pharmacokinetics study of EXM suspension and EXM SNEDDS was performed using a female waster rate. The developed formulation had a 37.65± 5.08 nm size and a 21.57±0.73 sec of self-emulsification time. Cmax of EXM suspension and EXM SNEDDS was found to be 122.49±8.27 and 194.86 ± 14.75 ng/mL, respectively. AUC0-720 of EMX SNEDDS was 1.71 times higher compared to EXM suspension, indicating that lipid nanoparticles improve the drug concentration in the plasma. So we conclude that SNEDDS improves the pharmacokinetic of EXM, which subsequently improves oral bioavailability.

DISSOLUTION ENHANCEMENT OF TETRAHYDROCURCUMIN USING OPTIMIZED SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM

Objective: The objective of this study was to optimize and enhance the dissolution of tetrahydrocurcumin (THC) using optimized self-nanoemulsifyingdrug delivery system (SNEDDS).Methods: The optimization was carried out with the D-optimal design using software design expert 7.15. The independent variables were the amountof oil, surfactant, and cosurfactant. The dependent variables were the emulsification time, percentage transmittance, and dissolution efficiency atminute 15 (DE15). The dissolution profile of the THC in optimum formulation compared with the unmodified THC.Results: The optimum formulation of SNEDDS consists of 10% Labrafil, 80% Kolliphor:Labrasol (1:3), and 10% PEG 400. The DE15 was 49.45%,significantly higher than the THC unmodified (p<0.05). The estimated responses were not significantly different from the experimental responses.The droplet size of the optimum formula was 53.8 nm, the polydispersity index was 0.043 and the zeta value was -19.4 mV.Conclusion: The D-optimal design was successfully determining the optimum formula of THC loaded SNEDDS. The SNEDDS formulation wasincreased the dissolution of THC.

Isolation, Formulation, and Efficacy Enhancement of Morin Emulsified Carriers Against Lung Toxicity in Rats.

The present study demonstrates a preparative medium-pressure liquid chromatography (MPLC) method for isolation of Morin besides evaluating its efficacy in comparison with its self-nanoemulsifying drug delivery (SNEDD) and nanoemulsion (NE) systems against in-vivo HgCl2-induced lung toxicity in rats. Morin was isolated from hydroalcoholic (70%) extract of Psidium guajava leaves by MPLC. The purity (> 90%) was done using HPLC. Screening of Morin solubility was studied to identify the components of each system. The prepared formulae were assessed for their thermodynamic stability, rheological properties, emulsification time, size, zeta potential beside its dissolution. The selected formulae according to the smallest size, highest zeta potential, and release at Q10min were assessed for their morphology by transmission electron microscopy (TEM) and protective potential against in-vivo HgCl2-induced lung toxicity in rats. All formulae were stable with Newtonian flow, emulsification time was (< 134 ± 10s), size (< 40nm) with zeta potential (> - 10.36 ± 0.99mV). The extent of free Morin dissolved from capsule showed significantly the lowest percent released (22.21 ± 1.45%) while in case of SNEDDs and NEs (> 55% dissolved). The morphology of the selected Morin formulae showed spherical shape within the nano-range. Supplementation of Morin and its formulae to rats caused significant decrease in C-reactive protein, hepatoglobin, hydroproxide, lung nitric oxide, tumor necrosis factor-α, immunoglobulin (E and G), histamine, malondialdehyde, and interleukin-6 gene expression while significant increase in immunoglobulin A, caspase-3, catalase, and glutathione peroxidase compared to HgCl2. SNEDD and NE formulae could ameliorate lung toxicity in a mechanism related to their antioxidant and anti-inflammatory potential.

Bioavailability Assessment of Vitamin A Self-Nanoemulsified Drug Delivery Systems in Rats: A Comparative Study

Objectives: To assess and compare the bioavailability of three different oral dosage forms of vitamin A in rats. The formulations included vitamin A self-nanoemulsified drug delivery (SNEDD) optimized formulation-filled capsule (F1), vitamin A SNEDD optimized formulation compressed tablet (F2) and vitamin A oily solution-filled capsules without any additives (control, F3). Materials and Methods: Bioavailability was assessed after a single oral dose of the three formulations using three groups of rats, each group comprising 6 rats. Blood samples were collected at baseline and over the next 8 h. Plasma was separated and extracted to obtain the drug, which was measured by HPLC. Statistical data analysis was performed using the Student t test and ANOVA with p < 0.05 as the minimal level of significance. Results: From the pharmacokinetic parameters, both F1 and F2 showed improved bioavailability compared to F3. The values of AUC ± SD were 3,080.7 ± 190.2, 2,137.1 ± 130.5 and 1,485.2 ± 80.1 ng·h/ml for F1, F2 and F3, respectively. The T_max was 1 h in case of F1 and F2 as compared to 1.5 h for F3. The C_max ± SD was 799.5 ± 48.5, 656.2 ± 64.4 and 425.8 ± 33.1 for F1, F2 and F3, respectively. The increase in AUC, C_max and T_max was significant (p < 0.05). The bioavailability calculated from the AUC for F1 and F2 relative to F3 was 207.4 and 143.8%, respectively. The bioavailability increased almost twofold and 1.4 times for F1 and F2, respectively. Conclusions: The study showed that the newly developed vitamin A SNEDD formulations increased the rate and extent of drug absorption compared to the oily drug solution. The present investigation demonstrated that vitamin A SNEDD optimized formulations, either as filled capsules or as compressed tablets, were superior to its oily solution with regard to their biopharmaceutical characteristics.