Percentage Drug Entrapment Efficiency Research Articles

Formulation Optimization and Characterization of Tizanidine Hydrochloride-Loaded Gold Nanoparticles Using Quality by Design Approach.

Gold nanoparticles (GNP) have been used extensively in cancer biologics and as drug carrier systems for improved pharmacokinetics and effective therapeutic action. GNPs also ensure reliable diagnosis with sensitive imaging. This study aimed to synthesize tizanidine hydrochloride (TZN)-biodegradable gold (Au) nanoparticles by the reduction of chloroauric acid (HAuCl4) with trisodium citrate using a microwave synthesizer and quality by design approach. The formulation method used was optimized using a 32 (two-factor, three-level design) factorial experiment. Temperature (X1) and concentration of gold salt (X2) were the two independent factors, and particle size (Y1), Percent drug entrapment efficiency (Y2), and polydispersity index (Y3) were the responses recorded for the study. The results of the study revealed that the optimized nanoparticles (TGN8) had a particle size (Y1) of 195 ± 1.2 nm, a polydispersity index of 0.2, and entrapment efficiency of 99.0 ± 2.9% at an optimized concentration of 14 mM gold salt (X1) and 100 0C temperature (X2). Atomic Force Microscopy showed the spherical shape particles. In vitro drug release was found to be 62.1 ± 0.5% release of TZN in simulated gastric buffer (pH 1.2) and 45.5 ± 2.8% in physiological buffer (pH 7.4). Overall, the study identified the optimal formulation conditions for TZN GNPs by considering the effects of independent variables on desired responses.

Formulation, Design, Optimization, and Characterization of Novel Long-acting Injectable Dosage Form of Anti-Psychotic Drug

Background: The current research aimed to create and analyze a new long-acting Brexpiprazole (BRX) injectable for successful anti-psychotic drug therapy in order to decrease dosage frequency and increase patient compliance. Systems for drug transport to particular body sites or regulating release rates with accuracy are known as drug delivery systems (DDS). By affixing the drug to a carrier particle like liposomes, nanoparticles, microspheres, etc., which modifies the drug's absorption and release properties, using carrier technology, drugs may be delivered in an intelligent manner. Methods: Utilizing Resomer RG 502 H and RESOMER® RG 752 H extended-release Polymer, Using a quasi-emulsion solvent diffusion, microspheres were made, and emulsification and solvent evaporation process. Results: The produced microspheres were assessed for stability tests, in vitro drug release, flow characteristics, and drug entrapment efficiency. FTIR experiments were used to establish how well the drug excipients worked together. The acarbose microspheres that were created had an 89.9 to 96.1 percent drug entrapment efficiency. The impact of factors like polymer content on medication release was studied. The Stability study of the formulation was carried out under different conditions, and data were established. Comparative pharmacokinetic studies between marketed oral formulation and Brexpirazole microsphere test formulations in Wistar/SD Rats were carried out and concluded. Conclusion: Brexpiprazole (BRX) novel long-acting injectable formulation, could be used effectively for the treatment of mentally challenged anti-psychotic patients worldwide. result: The acarbose microspheres that were created had an 89.9 to 96.1 percent drug entrapment efficiency. The impact of factors like polymer content on medication release was studied. The Stability study of the formulation was carried out under different conditions and data were established. Comparative pharmacokinetic studies between marketed oral formulation and Brexpirazole microsphere test formulations in Wistar/SD Rats were carried out and concluded. conclusion: Based on Literature data and drug excipients compatibility polymers were selected for manufacturing of extended release brexpiprazole microsphere Formulation. Preliminary formulation trial batches were taken with different polymers and studied for Drug Entrapment Efficiency and In Vitro release of drugs. Drug entrapment efficiency data of all the formulations are found satisfactory. In vitro, release results are compared with each formulation and based on the data, trial batch B1 with RESOMER® RG 502 H Poly(D,L-lactide-co-glycolide) 50:50 polymer and trial batch B2 with RESOMER® RG 752 H Poly(D,L-lactide-co-glycolide) 75:25 polymer have satisfactory results. So based on the study RESOMER® RG 502 H Poly(D,L-lactide-co-glycolide) 50:50 and RESOMER® RG 752 H Poly(D,L-lactide-co-glycolide) 75:25 were selected for Polymer Concentration and Formulation optimization study. The formulation is kept in the stability at different conditions and based on the data, the formulation is robust and all the derived values are found satisfactory. The comparative pharmacokinetic study was performed using oral marketed formulation and Brexpiprazole microsphere formulation. Based on the data we can conclude that long-acting depot formulations for administration of Brexpiprazol microsphere may offer no first-pass effect, increased bioavailability, fewer fluctuations in blood concentration and time, less dosing frequency, less no gastrointestinal intolerance, noninvasiveness.

Development, optimization, and assessment of losartan nano-bilosomes to mitigate diabetes-induced microvascular complications in Sprague Dawley rats

Losartan has a significant renal protection effect in type 2 diabetic patients. It was loaded into bilosomes to overcome its low oral bioavailability and improve its renal protective effects. The bilosomes were optimized using a 23 factorial design. Bile salt type and concentration and phospholipid concentration influenced the vesicles percent drug entrapment efficiency (%EE), vesicle size (VS), polydispersity index (PDI) and zeta potential (ZP). The %EE varied from 71.73 ± 0.91 % to 92.34 ± 0.75 %. VS varied from 146.87 ± 3.56 to 286.29 ± 1.72 nm while PDI ranged from 0.28 ± 0.02 to 0.46 ± 0.03. ZP was high enough (−28.34 ± 0.61 to −35.64 ± 1.38 mV) to afford colloidal stability to the bilosomes. The bilosomes had the ability to prolong the release of the drug, with the percentage of losartan released after 12 h ranging from 64.31 ± 1.03 % to 88.48 ± 0.93 %. An optimized formulation was selected and used orally in an in vivo diabetic nephropathy rats model to study its ability to improve losartan nephroprotective effects. The diabetic group exhibited elevated serum creatinine, blood urea nitrogen (BUN), urine albumin, and inflammatory cytokines. Losartan bilosomes demonstrated reduced BUN and proteinuria compared to the free drug. Additionally, they outperformed the free drug in enhancing kidney function, preserving renal cellular structure, and mitigating diabetic renal inflammation and fibrosis. This was evidenced by significantly lower levels of tumor necrosis factor-alpha, interleukin-6, nuclear factor kappa, and macrophage markers. These findings conclusively demonstrate the promising potential of losartan bilosomes as an effective oral formulation to mitigate diabetic nephropathy.

In vitro and Ex vivo Analysis of Pitavastatin-Loaded Liposomes for the Treatment of Hyperlipidemia

Pitavastatin is a BCS class II drug with low solubility and high permeability. So, the purpose of the study was to develop and characterize pitavastatin-loaded liposomes to achieve sustained release of the drug by increasing the solubility as well as bioavailability in treating hyperlipidemia. All formulations were prepared using the ether injection method (EIM) to determine the effect of three independent factors lecithin, cholesterol, and chitosan/PEG-6000 on two dependent variables of percent drug entrapment efficiency (% DEE) and percent cumulative drug release (% CDR) at low (-1) and high (+1) levels, respectively. The prepared liposomes were analyzed using various techniques, including percent DEE, percent CDR, FTIR, S0EM, and zeta potential. After 8 hours of dissolution, the lowest and highest drug releases were 78.01 and 88.70 percent, 68.12 and 80.19 percent, and 66.22 and 78.91 percent, for FCH-4 and FCH-2, FLE-1 and FLE-3, and FPEG-4 and FPEG-3, respectively. Additionally, permeability experiments were conducted by in vitro and ex vivo methods. The particle size of liposomes was between 3.51 μm to 4.19 μm that gave evidence of the formation of uni-lamellar vesicles. The release kinetics were investigated using a variety of mathematical models. SEM and FTIR analyses indicated that liposomes have a spherical and smooth surface with no interaction between medications and excipients. Comparative in vitro and ex vivo studies demonstrated that pitavastatin calcium-loaded liposomes may be viable for patients with hyperlipidemia due to their enhanced solubility and bioavailability. Dhaka Univ. J. Pharm. Sci. 22(1): 43-54, 2023 (June)

Binary ethosomes for the enhanced topical delivery and antifungal efficacy of ketoconazole

This work aimed to prepare ketoconazole-loaded ethosomes and binary ethosomes to improve its skin delivery and antifungal efficacy. A 32 factorial design was used to optimize the ethosomes and formulate ketoconazole-loaded binary ethosomes. Ethosomes and binary ethosomes were evaluated for particle size, polydispersity index, zeta potential, percent drug entrapment efficiency, drug release, skin permeation and deposition and antifungal efficacy. The ethosomes particle size ranged from 78.99±16.72 to 321.53±10.41 nm and decreased by increasing phospholipid and ethanol concentrations. The polydispersity index values were in the range of 0.17±0.01 to 0.49 ± 0.04. The percent drug entrapment efficiency ranged from 36.09±2.66 to 95.89±0.19 and increased by increasing phospholipid concentration while ethanol concentration had the opposite effect. The binary ethosomes had smaller size but similar drug entrapment efficiency and zeta potential compared with the ethosomes. They had significantly higher percent drug release (∼96%) and permeation (∼95%) through rat skin compared with the ethosomes (93% and 90%, respectively). Binary ethosomes and ethosomes had, respectively 1.9 and 1.8-fold higher drug skin permeation and 5.3- and 5.6-fold higher drug deposition in the epidermis/dermis compared with the drug suspension. The antifungal efficacy of the drug-loaded ethosomes and binary ethosomes were similar to the drug hydroalcoholic solution. Collectively, these results confirm the potential of these nanocarriers to enhance drug efficacy given their small size, sustained drug release and enhanced skin permeability.

DEVELOPMENT AND IN VITRO EVALUATION OF PHYTOSOMES OF ELLAGIC ACID

Objectives: The main objective of the present work is to enhance the bioavailability of ellagic acid (EA) by increasing its dissolution there by allowing for the exploitation of its therapeutic effects. Methods: Phytosomes containing EA were prepared by anti-solvent precipitation method. The prepared phytosomes were evaluated for drug entrapment efficiency, in vitro drug release, and drug excipient interaction studies. Results: Formulation F2 containing EA and soya lecithin in the ratio (1:2) showed highest percentage of drug release as 85.40% in 60 min and 95.86% in 120 min. The drug entrapment efficiency values were satisfactory. There were no interactions between the drug and the excipients used in its preparation according to Fourier-transform infrared spectra of pure EA and EA phytosomes. Conclusion: Phytosomes of EA were successfully produced by anti-solvent precipitation method and the percentage drug entrapment efficiency was satisfactory in almost all formulations. Formulation F2 exhibited highest percent of drug release as 85.40% in 60 min and 95.86% in 120 min to possess optimum bioavailability.

TPGS-chitosan conjugated mucoadhesive micelles of brinzolamide for glaucoma therapy: In vitro and in vivo evaluation

Micelle is a promising avenue for ophthalmic drug development technology and an especially suitable choice for hydrophobic drugs. The aim of this investigation was to synthesize Brinzolamide (BRZ) loaded d-alpha-tocopherol polyethylene glycol succinate (TPGS) - Chitosan conjugated micelles (BTCM) prepared by solvent evaporation method and to investigate their intraocular pressure (IOP) reducing efficacy for the management of glaucoma. The formulated BTCM was evaluated with various parameters such as size, zeta potential, morphology, percentage drug entrapment efficiency, drug loading capacity, and mucoadhesion strength, in-vitro and ex-vivo release. In-vivo anti-glaucoma efficacy study was conducted by glucocorticoid-induced glaucoma rabbit eye model and evaluated with the Marketed formulation (MF). The optimized formula showed a micelle size of 74.32±1.46 nm, and suitable physicochemical properties and in-vitro release mechanism were observed in that biphasic erosion-diffusion pattern of BRZ releases up to 8 h. The Ex-vivo corneal penetration of BRZ from BTCM showed a higher permeability rate than MF. Additionally, BTCM showed sustained release of BRZ, better corneal tissue compatibility, and improved anti-glaucoma potential, as compared to MF. The results concluded that BTCM is the suitable option for anti-glaucoma therapy because of its capability to improve ocular mucoadhesion of loaded BRZ via the interaction with the mucous membrane of the corneal surface.

A novel RP-HPLC method development and validation for simultaneous quantification of gefitinib and resveratrol in polymeric hybrid lipid nanoparticles and glioma cells

Resveratrol and Gefitinib are adjunct therapies for various cancers; however, both have been limited by low solubility, low cellular uptake, and bioavailability issues. As a result, this research aimed to develop an accurate, precise, selective, and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) method to simultaneously determine both compounds in nanoformulation and Glioma cells. The phenomenex luna C8 column, a mobile phase (80: 20 ratios of acetonitrile: 200 mM ammonium acetate) with a flow rate of 1 mL. min−1, 40 ± 0.2 °C as a column temperature, and the injection volume was 20 μl were selected as optimized chromatographic conditions. Retention time (RT) of resveratrol (1.80 min) and gefitinib (2.56 min) were identified using an optimized analytical method and detected at 345 nm (isosbestic point). The approach was proven to be specific for resveratrol and gefitinib analysis in the existence of PHLNPs, precise (RSD 2 %), and accurate (>90 %). The simultaneous analytical method was successfully developed to identify percentage drug entrapment efficiency (% DEE), % drug loading (% DL) of resveratrol and gefitinib in PHLNPs, and secondary estimates of in-vitro drug release profile and percentage cellular uptake studies. The in-vitro results revealed that the developed analytical method could simultaneously detect and quantify these drugs in other nanoformulations and in-vivo studies.

Design, development and evaluation of ketotifen fumarate solid lipid nanoparticles

The aim of the present study is to develop Ketotifen Fumarate solid lipid nanoparticles and to evaluate them. Suitable lipids (Tristearin, GMS and Campritol), stabilizer (Soy lecithin) and surfactant (Polaxomer) were selected. FT-IR studies were carried to check drug-excipient compatibility. In the present study nine formulations were formulated by using three prepared by hot homogenization followed by ultra-sonication technique. The nanoparticles were evaluated for particle size, PDI, zeta potential Drug content, percentage drug entrapment efficiency, in vitro drug release studies, release kinetics. FT-IR drug-excipient compatibility studies were revealed that there was no interaction between drug and selected lipids. The particle size ranged from 120.4 to 359.5 nm, PDI of all formulations were good within the range of 0.410 to 0.856, zeta potential ranged from -11.25 mV to -26.5 mV, Percentage drug entrapment efficiency of all formulations were observed were in the range of 78.88 to 93.67%. The cumulative percentage release of Ketotifen Fumarate from different formulations varied from 76.61 to 93.88%. Among all formulations, the formulation F1 showed highest drug release of 93.88% and considered as optimized formulation. The release kinetic studies showed that the release was first order (R2= 0.9123) diffusion controlled and the ‘n’ value obtained from the Korsmeyer-Peppas model indicated the release mechanism was Anomalous diffusion (non-fickian type) (n-value of F1 was 0.613). The developed SLNs were able to sustain the drug release for 12hrs.

Formulation and Characterization of Modified Release Microspheres of Lornoxicam Using Okra Gum as Natural Polymer and Ethyl Cellulose as Synthetic Polymer

Objective: The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their demonstrated efficacy in reducing pain and inflammation. The arthritis, pain and inflammation are effectively treated with Lornoxicam, an effective NSAIDs. Because the drug is weakly acidic, it is absorbed easily in the GI tract, and has a short biological half-life of 3 to 5 hours. To meet the objectives of this investigation, we developed a modified release dosage form to provide the delivery of lornoxicam at sustained rate which was designed to prolong its efficacy, reduce dosage frequency, and enhance patient compliance. The present research work was focused on the development of lornoxicam microspheres using natural polymer like okra gum extracted from the pods of Abelmoschus esculentus Linn. and synthetic polymer like ethyl cellulose along with sodium alginate prepared by Ca2+ induced ionic-gelation cross-linking in a complete aqueous environment were successfully formulated.
 Materials and Method: The microspheres were prepared by using sodium alginate with natural polymer (okra gum) and synthetic polymer (ethyl cellulose) in different ratios by Ca2+ induced ionic-gelation cross-linking. The formulations were optimized on the basis of drug release up to 12 hrs. The physicochemical characteristics of Lornoxicam microspheres such as drug polymer interaction study by Fourier Transform Infrared (FTIR) and further confirmation by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). The formulated microspheres were characterized for particle size, percentage drug entrapment efficiency, micromeritic properties, surface morphology, percentage swelling index, in-vitro drug release study and mechanism of drug release.
 Results and Discussion: The FTIR Spectra revealed that there was no interaction between polymer and Lornoxicam which was further confirmed by DSC and XRD. All the formulated Lornoxicam microspheres were spherical in shape confirmed by SEM. The microspheres exhibited good flow properties and also showed high percentage drug entrapment efficiency. All the batches have excellent flow properties with angle of repose in the range of 25.38° ± 0.04 to 30.41° ± 0.07, carr’s index and hausner’s ratios in the range of 10.40% ± 0.018 to 16.66% ± 0.012 and 1.128 ± 0.09 to 2.225 ± 0.01, respectively. The optical microscopic studies revealed that the mean particle size of all the formulations were found in the range of 819.46 ± 0.07 to 959.88 ± 0.02 μm and percentage of drug entrapment were found to be between 72.35 ± 0.02 to 90.00 ± 0.05. Swelling index of prepared microspheres revealed that with increasing the polymer ratios, there were increase in the swelling of prepared microspheres, showing in the range of 600.76 ± 0.42 to 690.11 ± 0.03% for okra gum microspheres at the end of 9 hr in comparison with ethyl cellulose microspheres which ranges between 179.71 ± 0.07 to 227.73 ± 0.05% at the end of 7 hr. In-vitro drug release of prepared microspheres formulation code LSO4 and LSE4 were found to be 88.654 ± 0.25% and 93.971 ± 0.20% respectively at the end of 12 hr. It was suggested that increase in polymer concentration, the drug release from the prepared microspheres got retarded producing sustained release of lornoxicam. In-vitro drug release data obtained were fitted to various release kinetic models to access the suitable mechanism of drug release. Drug release from lornoxicam-loaded alginate-okra gum microspheres followed a pattern that resembled sustained release (Korsemeyer-Peppas model) (R2 = 0.9925 to 0.9951), and n ≤ 1 indicated anomalous diffusion (non-Fickian), supercase-II transport mechanism LSO4 (n = 1.039) over a period of 12 hour underlying in-vitro drug release. Moreover, zero order model (R2 = 0.9720 to 0.9949) were found closer to the best-fit Korsemeyer - Peppas model.
 In addition, the drug release from lornoxicam-loaded alginate-ethyl cellulose microspheres also follow Korsemeyer-Peppas model (R2 = 0.9741 to 0.9973) with near to Hixson-Crowell model (R2 = 0.9953 to 0.9985) and n < 1 indicated non-Fickian diffusion or anomalous transport mechanism. Moreover, first order model with non-Fickian diffusion mechanism (R2 = 0.9788 to 0.9918) were found closer to the best-fit Korsemeyer-Peppas model/ Hixson-Crowell model.
 Conclusion: The present study conclusively demonstrates the feasibility of effectively encapsulating Lornoxicam into natural polymer (okra gum) and synthetic polymer (ethyl cellulose) to form potential sustained drug delivery system. In conclusion, drug release over a period of 12 hrs, could be achieved from these prepared microspheres. A pH-dependent swelling and degradation of the optimized microspheres were also observed, which indicates that these microspheres could potentially be used for intestinal drug delivery.

Preparation of Sterculia foetida-pullulan-Based Semi-interpenetrating Polymer Network Gastroretentive Microspheres of Amoxicillin Trihydrate and Optimization by Response Surface Methodology

In this study, a novel Sterculia foetida and pullulan-based semi-interpenetrating polymer network gastroretentive microsphere formulation was prepared using the emulsion crosslinking method and optimized by central composite design. The effects of the amounts of glutaraldehyde, S. foetida, and pullulan on the percent drug entrapment efficiency (EE), percent mucoadhesion at 12 h, and percent in vitro drug release at 12 h were optimized. The microspheres were characterized using scanning electron microscopy, fourier transform infrared spectroscopy, and differential scanning calorimetry. The formulation containing 4% v/v glutaraldehyde, 8.28% w/v pullulan, and 2.14% w/v S. foetida had 88.75±1.18% EE, 80.43±1.2% drug release at 12 h, and 81.73±1.50% mucoadhesion at 12 h, which was considered optimum and was used in an in vivo radiographic study. Semi-interpenetrating polymer network microspheres loaded with amoxicillin trihydrate were successfully prepared using S. foetida and pullulan. The prolonged retention of microspheres in the stomach with sustained drug release could effectively act against Helicobacter pylori reservoirs in the stomach and improve the therapeutic effect of amoxicillin trihydrate against H. pylori.

Formulation and molecular docking simulation study of luliconazole nanosuspension–based nanogel for transdermal drug delivery using modified polymer

The purpose of study was to formulate nanosuspension-based nanogel of luliconazole (LLZ) for transdermal delivery to enhance its skin retention and effectiveness using modified starch ester. Nanosuspensions show promising results with size of 369.1–745.4 nm having PDI 0.193–0.344 and zeta potential 22–45 mV. These nanosuspensions form micelles and hydrophobic core of it provides the reservoir for LLZ with better drug loading and binding interaction. Drug loading was confirmed by percent drug entrapment efficiency (PDEE) and PDI. Molecular docking simulation (MDS) provides detail insight of LLZ polymer complexation at hydrophobic cavity of micelles and revealed that there was binding between drug and polymer in aqueous milieu having interaction energy ranges from −7.1 to −6.0 kcal/mol. Nanosuspensions so made were incorporated into gel by using Carbopol 934 ® and tested for % drug content, spreadability, pH, and viscosity with ranges of 101.62–97.71, 28.94–34.38 (gcm/s), 6.91–7.21, and 4802.62–9461.83 (cp), respectively. Nanogel also evaluated for stability and skin permeation study using human cadaver skin (HCS). In vitro skin permeation study indicated that the amount of LLZ permeated through skin from nanogel (71.042–83.818 μgcm −2) was higher than standard cream (70.085 μgcm −2). Nanogel increased the accumulation of LLZ in HCS ~3 times than standard cream. The transdermal flux was greater for standard cream (123.79 μgcm −2), whereas smaller for nanogel (50.394–82.743 μgcm −2) due to skin retention. Nanosuspension-based gel are able to especially favor LLZ accumulation into skin, provide better drug loading, improve stability, and efficacy. Thus, targeting older antibiotics such as LLZ and formulating into nanosystem utilized to expand its usefulness to physicians to treat illnesses caused by resistant fungal strains.

A COMPARATIVE ASSESSMENT OF VESICULAR FORMULATIONS: TRANSFERSOMES AND CONVENTIONAL LIPOSOMES LOADED IVABRADINE HYDROCHLORIDE

Objective: Ivabradine hydrochloride (IH), a benzazepine derivative used to treat cardiovascular disease angina pectoris. In this study IH-loaded novel carrier systems transfersomes (TFs) and conventional liposomes (CLs) were developed and compared for their efficacy to enhance the stability of drugs from degradation.
 Methods: TFs formulations (TF-1, TF-2 and TF-3) were prepared by using different biocompatible surfactants; tween-80 (TW), span-80(S) and sodium deoxycholate (SC) in the concentration ratio of 15 parts with 85 parts of soy phosphatidylcholine as phospholipid by thin-film hydration method. These vesicles were compared with CLs formulation (L-1) prepared in 7:3 molar ratio of soy phosphatidylcholine: cholesterol by following the same method. These vesicles were compared for physical appearance, vesicle shape, and size, percentage drug entrapment efficiency (%DEE), deformability index (DI), in vitro percentage cumulative drug release study, and physical stability studies. The chosen optimized novel carriers were observed under scanning electron microscopy.
 Results: The compared data demonstrated that the physical appearance for all vesicles was turbid and had a spherical shape. The size distribution was in the range of 129.0 nm to 273.5 nm in vesicles. The %DEE (79.0±0.94) and DI (35.0±1.9) was found maximum in TF-1 formulation that was 2.3 times higher than L-1 formulation. The in vitro percentage cumulative drug release study followed second-order polynomial kinetics that was 2.0 times higher than L-1and 2.9 times higher than the plain drug in 30 min (90.4±0.06%) from TF-1. The vesicles were found to be stable at refrigeration conditions.
 Conclusion: Thus, amongst of all vesicles TW loaded TFs (TF-1) was chosen as an excellent novel vesicular carrier for hydrophilic drugs due to its higher deformability behavior than CLs that protects the certain drugs from biodegradation and provides stability.

Development and in vitro evaluation of domperidone/Dowex resinate embedded gastro-floatable emulgel and effervescent alginate beads

This work aims to develop and evaluate buoyant beads embedded with domperidone/Dowex 50WX2 resinate complex as novel multiple-unit type oral gastro-retentive drug delivery system. Domperidone (BCS II) has been chosen for gastric retention as it has a poor oral bioavailability (around 15%), a short biological half-life, and pH-dependent solubility with poor solubility at a high pH and good solubility at low pH. Two different techniques were used to induce beads buoyancy; first, formulation of effervescent beads by incorporation of NaHCO3 in the beads, which will release carbon dioxide gas upon reaction with the acidic gastric fluid causing the beads to float. Second, is the formation of low-density emulgel beads by the incorporation of light mineral oil in the beads. Resinate complex is used to control the drug release from the prepared formulations. Beads were evaluated for percent drug entrapment efficiency, floating behavior (float lag time and duration), mean particle diameter, in vitro drug release, and release kinetics in SGF. The effect of different concentrations of both NaHCO3 (1%, 2%, and 10%) and light mineral oil (2%, 5%, and 10%) on the floating behavior and physical appearance was studied. The optimized formula (F10) was subjected to a four-week stability study at both 25 °C and 40 °C. Results revealed that gastro-retentive beads possessed a floating duration of up to 24 h and no floating lag time was developed. The novel resinate loaded beads succeeded to sustain the release of domperidone in SGF. The optimized formula was stable at both temperatures of 25 °C and 40 °C for four weeks. Hence, the developed optimized formulation (F10) is considered as a potential to increase the domperidone bioavailability, decrease dosage frequency, and increase patient compliance.

Surface-modified polycaprolactone nanoparticles for the brain-targeted delivery of nevirapine

The low-density lipoprotein (LDL) receptors overexpressed in brain capillary endothelial cell (BCEC) membrane were successfully targeted by polysorbate 80 (PS80)-coated polycaprolactone (PCL) nanoparticles for brain delivery of nevirapine (NVP). The nanoparticles prepared by emulsion solvent evaporation technique were evaluated for mean particle size (nm), zeta potential (mV), percentage drug entrapment efficiency (% EE), percentage drug loading (% DL), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), in vitro drug release study, stability study and in vivo biodistribution study. The mean particle size (nm) of uncoated nanoparticles, NvPNPs5, and PS80-coated nanoparticles, P80NvPNPs5, were (128.43 ± 4.82) nm and (218.3 ± 7.3) nm, respectively. The SEM and TEM analysis showed small-sized (< 100 nm), spherical-shaped, smooth-surface nanoparticles with less aggregation. The zeta potential (mV) analysis showed stable nanoparticles with values (− 72.1 ± 0.00) mV, NvPNPs5; (− 16.2 ± 0.00) mV, P80NvPNPs5; (− 16.2 ± 0.00) mV, 6CFNvPNPs5; and (− 13.6 ± 0.00) mV, P806CFNvPNPs5. The FT-IR and DSC report indicated drug excipient compatibility. P80NvPNPs5 showed an in vitro drug release for 36 h and its release kinetic was best fitted in Higuchi model (R2 = 0.936). Korsemeyer Peppas model showed an anomalous non-Fickian drug release mechanism as n = 0.767. P80NvPNPs5 released NVP for 24 h in the brain with prolonged blood circulation for 48 h as compared with NvPNPs5 and free drug suspension, (p < 0.05) in in vivo biodistribution study in Swiss Wistar rat. The confocal laser scanning microscopy (CLSM) study showed uniform distribution of P80NvPNPs5 in rat BCECs for 24 h post i.v. administration. The present observation concludes the futuristic scope of P80NvPNPs5 nanoparticles for brain delivery of different antiretroviral drugs as well as other CNS active drugs to treat several CNS disorders.

Analytical method development and validation of reverse-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous quantifications of quercetin and piperine in dual-drug loaded nanostructured lipid carriers

Quercetin and piperine are often used as an add-on therapy for various diseases, however both drug exhibits poor aqueous solubility and photosensitivity issue. Therefore, the aim of the present study is to improve the pharmaceutical challenges by incorporating both the drugs in nanostructured lipid carriers (NLCs) and to develop a sensitive, selective, accurate and precise reverse-phase high performance liquid chromatography (RP-HPLC) method for the simultaneous analysis of both drugs in NLCs. Effective chromatographic separation of quercetin and piperine was achieved on Hypersil gold C-18 column and mobile phase consisting of a mixture of acetonitrile and HPLC grade water (pH 2.6, adjusted with 2%v/v glacial acetic acid) in an isocratic elution mode. The flow rate of the mobile phase was 1 mL/min, column temperature at 35 ± 0.2 °C and the injection volume was 20 μL. The retention time for quercetin and piperine were found to be at 2.80 min and 10.36 min, respectively and detected at an isobestic wavelength of 346 nm using a photodiode array (PDA) detector. The method was found to be specific for the simultaneous analysis of quercetin and piperine in presence of NLCs matrix, accurate (>90%) and precise (%RSD < 2%). The validated RP-HPLC method effectively utilised to determine the percentage drug entrapment efficiency cum percentage drug loading of quercetin and piperine in NLCs enriched formulations along with the secondary estimation of in vitro cumulative percentage drug release study. The results were found to be reliable, hence the validated RP-HPLC method could be further used for the simultaneous detection and quantification of both these drugs in other lipid-based nano-formulations such as solid-lipid nanoparticles, polymer-lipid hybrid nanoparticles, lipid drug conjugates, etc. in in vitro and in vivo.

Novel drug delivery system of luliconazole - Formulation and characterisation

Dermatophytes, a group of fungal species causing superficial fungal infections possess a major health problem in a wide group of people. Various approaches have been used in past for treatment of such infections but, owning to their low dermal permeability and less retention time, such formulations are proven to be less effective. Thus, to overcome such limitations, various novel drug delivery systems were developed. “Nanosponge” - a porous nano carrier system which can entrap drug of choice and improve its dermal availability, permeation rate and retention time is one such example. In the present study, a novel azole antifungal drug luliconazole, having wide spectrum of activity and potent against dermatophytes was used as model drug. It has low aqueous solubility and less dermal availability. A regular 2-level factorial design was applied using Design Expert® 11 software to formulate luliconazole loaded nanosponge drug delivery system using emulsion solvent diffusion method. Polyvinyl alcohol and ethyl cellulose were used as polymers. Formulated nanosponges were characterised for percentage entrapment efficiency, particle size, poly dispersibility index, zeta potential, surface morphology studies using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and porosity. Fourier transform infrared spectroscopy, X-ray diffraction and differential scanning calorimetric analysis were also carried out to confirm the encapsulation of the drug within the carrier. In vitro release studies and other relevant parameters were also determined. Further, prepared nanosponges were incorporated into gel base using carbomer 934 and characterised for viscosity, swelling behaviour, spreadability, in vitro diffusion studies, skin irritancy test, in vitro permeation studies using rat skin membrane, antifungal activity and stability studies. From the results obtained it was evident that, formulated nano carriers were in desired nano size range having characteristic porous structure which was further confirmed by SEM and TEM studies. It was perceived that percentage drug entrapment efficiency was in the range of 70–80%. Drug release kinetics data revealed prolonged release up to 8 h. Release pattern was found to be diffusion controlled which was confirmed by Higuchi's plot. In vitro permeation studies revealed enhanced permeation rate and skin retention time. Collectively, the developed drug delivery system had greater permeation rate and increased retention time. Further, the formulation was found to be non-irritant and stable. Overall, the aim of enhancing dermal availability and sustaining the release of drug for effective fungal therapy was achieved by formulating as nanosponge gel.

FORMULATION AND OPTIMIZATION OF MUCOADHESIVE MICROSPHERES OF VALSARTAN BY USING BOX-BEHNKEN DESIGN

Objective: The purpose of this study was to formulate and optimize mucoadhesive microspheres of antihypertensive drug (valsartan) within ethyl cellulose as a carrier polymer and carbopol 934P as a mucoadhesive polymer for controlling the release of valsartan.&#x0D; Methods: The emulsion solvent evaporation technique was used for preparation of microspheres of valsartan and the Box-Behnken design was employed with thee independent variables that is amount of ethyl cellulose (X1) and amount of carbopol 934P (X2) and stirring speed (X3) and evaluate four dependent variables such as percentage mucoadhesion, Q1 h, t90% and drug entrapment efficiency.&#x0D; Results: The optimum conditions were found to be X1= 200 mg, X2= 107 mg and X3= 1200rpm. The optimized batch exhibited a high drug entrapment efficiency of 85.63±1.384%, percentage mucoadhesion was 66.76±0.986% and drug release was also sustained for more than 12 h.&#x0D; Conclusion: The analysis of variance showed a significant effect of independent variables. The scaning electron microscopy (SEM) analysis showed that the microspheres were spherical and free-flowing. The microspheres of valsartan were stable after thee month stability study at accelerated condition.

FORMULATION AND OPTIMIZATION BY APPLYING 32 FULL FACTORIAL DESIGN OF MUCOADHESIVE MICROSPHERES OF NIFEDIPINE

Objective: The purpose of this research work is to formulate and optimize mucoadhesive microspheres of nifedipine using Carbopol 934P as mucoadhesive and ethyl cellulose as a carrier polymer for controlling the release of nifedipine.&#x0D; Methods: The emulsion solvent evaporation technique was used for the preparation of microspheres and the 32 full factorial designs were employed for optimization of microspheres. The developed microspheres were characterized for percent yield, entrapment efficiency, particle size, in vitro release study, percent mucoadhesion, surface morphology, and stability study.&#x0D; Results: Evaluating outcomes of preliminary batches indicated that 100 ml volume of processing medium, 5 h stirring time and 2% concentration of emulsifying agent were suitable for spherical, free-flowing microspheres and high percentage drug entrapment efficiency. The optimized batch exhibited 84.35% drug entrapment efficiency, 61.78% mucoadhesion and drug release were also sustained for more than 12 h. Scanning electron microscopy study revealed that produced microspheres were spherical in shape.&#x0D; Conclusion: Experimental responses of the optimized batch have close proximity with the predicted value and stability study of the optimized formulation proved the formulation is stable for a long period of time; hence, it is an excellent alternative over the conventional delivery system.

Synthesis of Biocompatible Double‐Tailed Nonionic Surfactants and Their Investigation for Niosomal Drug‐Loading Applications

AbstractNonionic surfactants are capable of self‐assembling and thus are of vital importance for designing various drug‐delivery systems. This study reports the synthesis, characterization, biocompatibility, and drug‐loading potential of sulfanilamide‐based novel nonionic surfactants. These surfactants were synthesized in a single‐step reaction and characterized using nuclear magnetic resonance (NMR), electron impact mass spectroscopy, and fourier‐transforminfrared spectroscopy (FTIR). Critical micelle concentration (CMC) of the synthesized nonionic surfactants was determined using a ultraviolet–visible (UV) spectrophotometer. The surfactant potential for niosomal vesicles was explored using simvastatin as a model drug. The drug‐loaded vesicles were screened for shape, size, size distribution, and percent drug entrapment efficiency (EE%) using atomic force microscopy (AFM), zeta potential, and UV–visible spectrophotometry. Biocompatibility of the synthesized surfactants was investigated through blood hemolysis and cell toxicity assays. Synthesized nonionic surfactants revealed lower CMC values of 0.045–0.095 mM and entrapped an improved amount of drug upon self‐simplifying in niosomal vesicles. Findings of the study confirm these nonionic surfactants as hemocompatible and nontoxic candidates for vesicular drug‐delivery applications.