Percentage Drug Research Articles

Supramolecular cyclodextrin-based reservoir as nasal delivery vehicle for rivastigmine to brain

The purpose of this study involved the synthesis of supramolecular reservoir (i.e. cyclodextrin metal-organic framework, MOF) using cyclodextrins as building blocks, followed by cross-linking to obtain crosslinked CD framework (CDF) using CD-MOF as template and functionalized with borneol (BO) to enhance rivastigmine (RIV) permeation and facilitate brain targeting via intranasal administration. Utilizing BO modified CDF (BO-CDF) with cubic shape as a carrier for the encapsulation of RIV, a nasal RIV delivery system (RIV@BO-CDF) was fabricated. The particle size of RIV@BO-CDF was approximately 250 nm, and the drug loading capacity reached 15 ± 2 %. BO-CDF improved the mucoadhesion and enhanced RIV permeability with the plasma concentration-time curve (AUC), the brain AUC and the peak drug concentration within brain in rats 1.7, 2.3 and 8 times than that of oral RIV solution, respectively. The relative drug targeting efficiency percentage (DTE, 139.4 %) and direct drug transfer percentage (DTP, 28.3 %) of RIV@BO-COF indicated good targeting efficiency and direct nose-to-brain drug delivery. Overall, this study provides a potential application of supramolecular cyclodextrin-based reservoir to enhance the brain targeting and efficacy of the RIV via nasal delivery.

Locust bean gum glutarate nanocomposite hydrogel microspheres of gliclazide: Optimization by box-Behnken design and preclinical evaluation of anti-diabetic efficacy

In this study, carboxymethyl locust bean gum was synthesized and nanocomposite hydrogel microspheres (GHMs) of gliclazide were produced based on nanosilicate reinforcement and aluminium-ion driven gelation process, followed by covalent crosslinking with glutaric anhydride (GA). The effect of three independent variables (polymer and GA concentration, incubation time) on the drug entrapment efficiency (DEE%) and percent drug release at 8 h, was optimized using Box-Behnken design. The highest DEE (%) and lowest drug release was achieved at the following optimized conditions: polymer (2.43 %), GA (0.34 %), and incubation (27 min). The nanoscilicate-enriched matrix provided a maximum of 75.13 % DEE, 92.33 % gel fraction, and excellent flowability. The optimized microspheres had virtually spherical morphology, according to FE-SEM analysis. FTIR study indicated a hydrogen bonding interaction between the drug and other formulation components. X-ray and DSC measurements suggested that the crystallinity of the drug decreased following integration into the matrix. The optimized GHM demonstrated anomalous diffusion of gliclazide in simulated gastrointestinal fluids for 12 h without disintegration. In streptozotocin (50 mg/kg BW)-induced diabetic rats, the optimized formulation diminished blood glucose level by about 72 % in 12 h. Thus, the nanocomposite GHMs created by combining nanosilicate with GA had an outstanding potential for long-term control of diabetes.

Modified Release Interpenetrating Polymeric Network Hydrogel Beads of Montelukast Sodium Via Box Behnken Design

Background: Interpenetrating Polymeric Networks (IPN) are cross-linked polymeric alloys developed when two or more cross-linked polymers inter-penetratingly entangle. Interpenetrating polymeric networks possess several benefits including stability, biocompatibility, biodegradability, high swelling ability, and modified release efficiency. Aim: The aim of this study is to design stable, control-released montelukast sodium-loaded IPN hydrogel beads as a promising approach toward drug delivery. Objective: The goal of the present work was to develop Chitosan (swellable polymer) and glutaraldehyde (cross-linker) based modified (controlled) released montelukast sodium IPN hydrogel beads. Methods: The montelukast sodium IPN hydrogel beads were prepared via the precipitation method, and the final batch of IPN hydrogel beads was based on particle size, percent entrapment efficiency, area of swelling, and cumulative percent drug release using an overlay plot in Box-Behnken design. Compatibility studies (DSC, FT-IR) and microscopical observation (SEM) confirmed the compatibility and sphericity of the formulations. Results: The optimized (comprising 2.01% chitosan and 0.48% glutaraldehyde) IPN hydrogel beads having satisfactory particle size (817.76±54.49 μm), good entrapment efficiency (71.36±3.04%), and area of swelling (27.00±1.68 mm2) showed swelling and pH-dependent controlled montelukast release (92.96±1.05%) after 12 h with longer duration of action. Conclusion: The prepared montelukast sodium IPN hydrogel beads could be a potent control-released drug delivery vehicle.

Optimization of Mesoporous Silica Nanoparticles of Silymarin through Statistical Design Experiment and Surface Modification by APTES

ABSTRACT: The major goal of this study was to create surface-modified mesoporous silica nanoparticles (MSN) of Silymarin, which has a short half-life and requires regular dosing due to first-pass metabolism. MSN was prepared by cost effective Sol-Gel method, functionalized by (3-Aminoprpyl) triethoxysilane (3-APTES). Evaluated and compared the Silymarin-loaded MSN and APTES functionalized MSN for drug loading, in-vitro dissolution, particle size, surface morphology, surface area, pore size and volume. The percent drug loading and encapsulation efficiency of APTES-functionalized MSN were found to be 92.50±0.72 % percent and 93.20±0.13 %, respectively, which showed a higher value in APTES-functionalized MSN as compared to Silymarin-loaded MSN. Drug release of APTES-functionalized MSN was 92.15 0.03%, which was more as compared to silymarin-loaded MSN. XRD showed that after functionalization silymarin changed from crystalline to amorphous form. SEM indicates that MSN was formed in a spherical shape with particle size of 196.7nm. The BET analysis proved that the nanoparticles had a larger surface area, which was reduced after drug loading and functionalization. Also, the pore size was increased and the pore volume was reduced after functionalization, indicating the incorporation of silymarin. The results suggested that the functionalization might successfully increase adsorption capacity, larger surface area, and increased encapsulation. Mesoporous silica nanoparticles also showed a greater impact on dissolution.

Design and Development of Solid Lipid Nanoparticles of Tofacitinib Citrate for the Treatment of Rheumatoid Arthritis: A Quality by Design Approach.

Solid lipid nanoparticles, or SLNs, have gained popularity recently as a possible drug delivery method. However, the idea of using SLNs for organ and site-specific drug administration is still in its early stages due to the difficulties associated with this approach. The aim of this study is to develop SLNs with improved pharmaceutical characterization and anti-arthritic efficacy. Tofacitinib citrate (TC)-loaded SLNs were created using the microemulsification method, with the addition of stearic acid, chitosan, and Tween 80 to improve skin permeability. Seventeen SLNs were developed and characterized for particle size, entrapment efficiency (EE), and percentage drug release according to the Box-Behnken design. The DSC analysis revealed a strong endothermic peak at 166.18°C, significantly different from the pure TC reported at 218.05°C. This indicates a notable alteration in the endothermic peak of the SLNs, demonstrating a relationship with the excipients used in this investigation. XRD study highlighted significant characteristic drug peaks at positions 21.06 and 23.63 (2ɵ). These peaks represented the modifications that were seen in pure TC. The SEM analysis of the optimized lipid nanoparticles showed a smooth surface and a spherical appearance. The particle size analysis of the optimized formulation showed an average size of 181.5 nm. Also, the polydispersity index (PI) revealed a value of 0.495, indicating homogeneous dispersion. The zeta value was 8.2 mV, indicating stability.

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.

Curcumin-loaded gold nanoparticles with enhanced antibacterial efficacy and wound healing properties in diabetic rats

Diabetic wounds pose a significant global health challenge. Although curcumin exhibits promising wound healing and antibacterial properties, its clinical potential is limited by low aqueous solubility, and poor tissue penetration. This study aimed to address these challenges and enhance the wound healing efficacy of curcumin by loading it onto gold nanoparticles (AuNPs). The properties of the AuNPs, including particle size, polydispersity index (PDI), zeta potential, percent drug entrapment efficiency (%EE) and UV–Vis spectra were significantly influenced by the curcumin/gold chloride molar ratio used in the synthesis of AuNPs. The optimal formulation (F2) exhibited the smallest particle size (41.77 ± 6.8 nm), reasonable PDI (0.59 ± 0.17), high %EE (94.43 ± 0.25 %), a moderate zeta potential (−8.44 ± 1.69 mV), and a well-defined surface Plasmon resonance peak at 526 nm. Formulation F2 was incorporated into Pluronic® F127 gel to facilitate its application to the skin. Both curcumin AuNPs solution and gel showed sustained drug release and higher skin permeation parameters compared with the free drug solution. AuNPs significantly enhanced curcumin’s antibacterial efficacy by lowering the minimum inhibitory concentrations and enhancing antibacterial biofilm activity against various Gram-positive and Gram-negative bacterial strains. In a diabetic wound rat model, AuNPs-loaded curcumin exhibited superior wound healing attributes compared to the free drug. Specifically, it demonstrated improved wound healing percentage, reduced wound oxidative stress, increased wound collagen deposition, heightened anti-inflammatory effects, and enhanced angiogenesis. These findings underscore the potential of AuNPs as efficacious delivery systems of curcumin for improved wound healing applications.

Formulation and evaluation of phytosomes containing bioactive from Carica papaya seeds

Background: Papaya seeds are a rich source of proteins, fat, fibers, vitamins, minerals, monounsaturated fatty acids, polyphenols, and powerful antioxidants like flavonoids. Low solubility limits the absorption and bioavailability of herbal constituents. Hence, phytosomes of Papaya seed extract were formulated to enhance its solubility and bioavailability. Methodology: Papaya seeds were extracted using ethanol as solvent, and all the phytoconstituents present in the extract were assessed during the phytochemical screening and LC-MS analysis. In-vitro antidiabetic activity pure extract was determined by alpha-amylase and alpha-glucosidase enzyme inhibitory assay. The phytosomes of extract were formulated using the lipid thin film formation method and Soya lecithin and Cholesterol as lipids. The formulated phytosomes were analyzed for parameters such as particle size, zeta potential, encapsulation efficiency, percent drug content, and In-vitro dissolution study. The chemical nature of the formulation was studied using FTIR analysis and powder X-ray diffractometry. Thermal stability of phytosomes analyzed with the help of Differential Scanning calorimetry. Results: LC-MS identified 16 phytoconstituents. In-vitro antidiabetic activity showed 59.97% and 51.17% inhibition of enzymes alpha-amylase and alpha-glucosidase, respectively. The encapsulation efficiency of the optimized formulation was 88.41±0.91% with a particle size of 188.0±53.7nm. TEM images of formulation confirm the formation of phytosomes. FTIR, DSC, and Powder X-ray diffractometry showed no unwanted peaks. The in vitro dissolution study showed 89.26±1.05% CDR of phytosome, while the extract showed 47.78±0.59% CDR. Conclusion: Evaluation results of phytosomes suggest that this formulation can be used as an effective herbal antidiabetic formulation

Design, development, and optimization of sumatriptan loaded ethosomal intra-nasal nanogel for brain targeting

Background: Sumatriptan is one of the most essential drugs for treating migraine. However, dosage-related side effects are still a worry despite its 14 % oral bioavailability and recurrence of migraine-associated diseases. Methodology: The fundamental focus of the study is to develop the sumatriptan intra-nasal nano-ethsomal gel by film hydration technique with the aid of QbD principles that govern the varied compositions and blends of polymers like HPMC K100M and Phospolipon 90G to develop a sustained release dosage form. Results and discussion: The preliminary FT-IR and DSC studies revealed no interactions between the drug and their physical mixtures. The present study considered three observable responses: vesicle size, zeta potential, and percent drug release after 24 h, taken into consideration during the optimization of the ethosomal formulations utilizing 32 central composite designs (CCD). The vesicle size (122.23 nm), zeta potential (-40.2 mV), and drug release percentage (92.61 %) for all formulations were seen in the F12 batch after 24h. The p-XRD and SEM studies indicated that the nano-ethosomal gel was stable. The stability studies indicated the preparation of a more stable formulation for the parameters under the study protocol. Conclusion: Using a novel intra-nasal brain targeting approach by adapting the film hydration technique, the current issues might be addressed, and the drug's duration of residence at the absorption site uptake substantially increase. To efficiently modify the drug's residence through the intra-nasal route, this work focuses on developing a nano-ethosomal gel loaded with sumatriptan.

Formulation and evaluation of extended-release floating tablets of labetalol hydrochloride 200 mg

The aim of present work is to formulate and evaluate extended-release floating tablets of Labetalol HCL to improve the bioavailability, Patient compliance and solubility on oral floating drug of Labetalol HCL. Labetalol HCL is mainly used in the treatment of hypertension, which is BCS Class Ⅰ drug i.e. Highly soluble and highly permeable. The tablets were prepared by wet granulation method by using different concentrations of HPMC polymer. The tablets were evaluated for Preformulation characteristics, Pre compression parameters and post compression parameters. In-vitro dissolution studies were performed for all prepared formulations by using dissolution test apparatus employing a paddle stirrer at 50 rpm and 37 ± 0.5°C, 0.1N HCL buffer was used as dissolution medium. Samples of 5ml each were withdrawn at different time intervals. Each sample withdrawn was replaced with an equal amount of fresh dissolution medium. Samples were diluted and assayed at 302 nm using Agilent UV Visible double beam spectrophotometer. The increased drug release is due to the presence of low concentration of HPMC K4 m. The drug release kinetics was calculated for all the formulations, among all the formulations F8 was taken as optimized formulation whose percentage drug release was found to be 96%. It indicates the release follows zero order and Hixon kinetics. Hence formulation F8 was Considered as the optimized batch and stability studies were conducted at 40oc±2oc/75±5%RH, Storage condition for 3 months and no change was observed.

Optimization and evaluation of modified release solid dosage forms using artificial neural network

This study aims to optimize and evaluate drug release kinetics of Modified-Release (MR) solid dosage form of Quetiapine Fumarate MR tablets by using the Artificial Neural Networks (ANNs). In training the neural network, the drug contents of Quetiapine Fumarate MR tablet such as Sodium Citrate, Eudragit® L100 55, Eudragit® L30 D55, Lactose Monohydrate, Dicalcium Phosphate (DCP), and Glyceryl Behenate were used as variable input data and Drug Substance Quetiapine Fumarate, Triethyl Citrate, and Magnesium Stearate were used as constant input data for the formulation of the tablet. The in-vitro dissolution profiles of Quetiapine Fumarate MR tablets at ten different time points were used as a target data. Several layers together build the neural network by connecting the input data with the output data via weights, these weights show importance of input nodes. The training process optimises the weights of the drug product excipients to achieve the desired drug release through the simulation process in MATLAB software. The percentage drug release of predicted formulation matched with the manufactured formulation using the similarity factor (f2), which evaluates network efficiency. The ANNs have enormous potential for rapidly optimizing pharmaceutical formulations with desirable performance characteristics.

Karanjin-loaded soya lecithin-based ethosomal nanogel for the therapeutic intervention of psoriasis: formulation development, factorial design based-optimization, in vitro and in vivo assessment

This study aimed to develop and optimize karanjin-loaded ethosomal nanogel formulation and evaluate its efficacy in alleviating symptoms of psoriasis in an animal model induced by imiquimod. These karanjin-loaded ethosomal nanogel, were formulated to enhance drug penetration into the skin and its epidermal retention. Karanjin was taken to formulate ethosomes due to its potential ani-psoriatic activity. Ethosomes were formulated using the cold method using 32 full factorial designs to optimize the formulation components. 9 batches were prepared using two independent variables X 1: concentration of ethanol and X 2: concentration of phospholipid whereas vesicle size (Y 1) and percentage entrapment efficiency (Y 2) were selected as dependent variables. All the dependent variables were found to be statistically significant. The optimized ethosomal suspension (B3) exhibited a vesicle size of 334 ± 2.89 nm with an entrapment efficiency of 94.88 ± 1.24% and showed good stability. The morphology of vesicles appeared spherical with smooth surfaces through transmission electron microscopy analysis. X-ray diffraction analysis confirmed that the drug existed in an amorphous state within the ethosomal formulation. The optimized ethosome was incorporated into carbopol 934 to develop nanogel for easy application on the skin. The nanogel underwent characterization for various parameters including spreadability, viscosity, pH, extrudability, and percentage drug content. The ethosomal formulation remarkably enhanced the skin permeation of karanjin and increased epidermal retention of the drug in psoriatic skin compared to marketed preparation and pure drug. A skin retention study showed that ethosomal nanogel formulation has 48.33% epidermal retention in 6 h. In vivo, the anti-psoriatic activity of karanjin ethosomal nanogel demonstrated significant improvement in psoriasis, indicated by a gradual decrease in skin thickness and scaling as reflected in the Psoriasis Severity Index grading. Therefore, the prepared ethosomal nanogel is a potential vehicle for improved topical delivery of karanjin for better treatment of psoriasis.

Effects of Distracted Parenting and Housing on Juvenile's Bullying Children

Background and Aim: This study aimed to find out the effect distracted parenting and housing that lead towards Juvenile's Bullying children Methods: Descriptive-correlational research design was used to study the impact of broken family, and housing factors on juvenile delinquency. Researcher used a Non – probability (purposive) sampling technique and selected one hundred juvenile offenders from Juveniles Bullying Station for data collection belonged to the age range between fourteen to eighteen years from 3th April to 10th November 2023. Present study explored various effects of juvenile delinquency related with broken family, and housing factors on juvenile. Reliability of instrument was determined through the use of Alpha Cronbach approach and the instrument validity was determined through a panel of experts. The analysis of the data was used descriptive statistics frequencies, percentages, mean, standard deviation and Analysis of Variance (ANOVA). In order to assess the effect distracted parenting and housing on Bullying children. Results: The findings of the present study reveal that indicate to high percentage theft (29%), drug abuse (21%), murder (16%) and rape (14%); while there is positive association among types of offenses committed by the juveniles with residence area (r=0.219), father married another woman (r=0.224), mother married another man (r=0.289), divorce (r=0.225), father death (r= 0.257) and mother death (r=0.246). Conclusion: The study concluded that there is positive association among types of offenses and misdemeanor committed by the juveniles with distracted parenting and housing.

QbD Assisted Systematic Review for Optimizing the Selection of PVP as a Ternary Substance in Enhancing the Complexation Efficiency of Cyclodextrins: a Pilot Study.

Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (Ks) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a βCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and β-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.

D-α-tocopheryl polyethylene glycol succinate-decorated dual drug-loaded lipidic nanocarriers: A strategic approach for targeting lymphatic uptake and p-gp efflux modulation to enhance oral bioavailability in HIV-1 viral reservoirs

The toxicity potential and inadequate bioavailability of antiretroviral therapy restrict their effectiveness in completely eradicating HIV-1 from viral reservoirs, as the drugs encounter difficulties in accessing these reservoirs. This study presents a combinatorial d-α-tocopheryl polyethylene glycol succinate (TPGS)-decorated nano-structured lipid carrier of Etravirine (ETR) and Darunavir Ethanolate (DRVE) that was formulated, optimized, and characterized to achieve synergistic effects against HIV-1 infection. The effectiveness of the combinatorial approach was evaluated by in silico studies, and their docking score and free binding energy showed that both drugs demonstrate synergistic effects against their respective enzymes. The cellular research of ED (ETR and DRVE) in TMZ-b1 cell lines also showed that the best ratio of ETR and DRVE (1:6.5 μg/mL) produced a combined effect. The formulation, termed ED-TPGS-NLCs, underwent optimization using central composite rotational design (CCRD) through a modified emulsification process, followed by characterization based on globule size, polydispersity index (PDI), percentage entrapment efficiency, percentage drug loading, and transmission electron microscopy (TEM) analysis. In vitro release studies demonstrated a notable improvement of drug release from the optimized lipid nanosystem, conforming to the Korsmeyer-Peppas kinetics model. Besides, the in-vitro studies, the intestinal permeation enhancement study, the intestinal depth analysis, and the pharmacokinetic assessment of the optimized formulation in Wistar rats were performed to improve permeation and increase plasma drug concentration. ED-TPGS-NLCs also stopped HIV-1 infection in TMZ-b1 cell lines by 50 %, and the lowest concentration needed to do this was about 58 times lower than purified ED suspension. These studies ensure that ED-TPGS-NLCs were taken up due to the formation of chylomicrons and inhibit the p-gp efflux system by TPGS and solutol to inhibit the first-pass hepatic metabolism, which helps to improve the intestinal permeation and enhance plasma drug concentration, leading to enhanced oral bioavailability of ED. Hence, the improved bioavailability of ED in the nanoformulation also enhanced the anti-retroviral efficacy and improved the safety margins of ED-TPGS-NLCs. These findings can also reduce the side effects of high doses of antiretroviral drugs.

Formulation and Evaluation of Betulin Loaded Transdermal Patches

Objectives: To develop and evaluate Transdermal patches of Betulin along with various polymers for controlled release action. Method: Suitable method such as Solvent Casting Technique of Film Casting Technique are used for preparation of Transdermal patch. Result: The prepared Transdermal patches were transparent, smooth, uniform and flexible. The method adopted for preparation of system was found satisfactory. Conclusion: Various formulations were developed by using hydrophilic and hydrophobic polymers like HPMC E5 and EC respectively in single and combinations by solvent evaporation technique with incorporation of penetration enhancer such as dimethylsulfoxide and dibutyl phthalate as plasticizer. Formulation F7 containing equal ratio of HPMC E5: EC (5:5) showed maximum percentage drug content 95.44%. A suitable UV Spectroscopy method for the analysis of Betulin was developed. Betulin showed maximum absorption at wave length 215 nm in isotonic phosphate buffer (pH 7.4) solutions. The pre-formulation studies involving description, solubility, melting point, partition coefficient of the drug were found to be comparable with the standard. The Transdermal patch of Betulin was prepared successfully by solvent evaporation method. Transdermal patch of Betulin for Transdermal drug delivery was evaluated. Calibration curve was obtained; Transdermal film was prepared, overcome limitations regarding bioavailability of drug was done. Keywords: Controlled DDS, Transdermal DDS, Betulin, Transdermal Patch, solvent evaporation method.

Fabrication and Characterization of Sustained-Release Eudragit RSPO Microsphere of Lornoxicam by Spray Drying Technique

Background: Lornoxicam is a potent non-steroidal anti-inflammatory drug (NSAID) with strong analgesic properties; however, its short half-life necessitates frequent administration for sustained efficacy. Objective: The objective of the present study was to identify critical formulation parameters affecting sustained release Eudragit RSPO microsphere of lornoxicam employing the concept of design of experiments Method: The lornoxicam-loaded microspheres were prepared using a spray drying technique by optimizing the drug:polymer ratio(X1) and inlet air temperature (X2) using a 32 full factorial design. The percentage drug entrapment (Y1), percentage yield (Y2) and cumulative percentage of the drug dissolved at 18 hr (Y3) were selected as dependent variables. Microspheres were evaluated for percentage drug entrapment, mean particle size, percentage yield, in vitro drug release study and scanning electron microscopy (SEM). Result: The optimized batch showed 84.51% drug release after 18 h with significantly higher drug entrapment and percentage yield. The optimization was further verified using overlay and desirability plots. The sustained release behavior of the drug from microspheres in GIT was displayed. The predicted and observed responses for the optimized formulation were in close agreement with the release profile of the drug. Conclusion: The sustained release microspheres of lornoxicam may prove to be an effective analgesic with excellent anti-inflammatory potential.

Verapamil-Loaded Cubosomes for Enhancing Intranasal Drug Delivery: Development, Characterization, Ex Vivo Permeation, and Brain Biodistribution Studies

Verapamil hydrochloride (VRP), an antihypertensive calcium channel blocker drug has limited bioavailability and short half-life when taken orally. The present study was aimed at developing cubosomes containing VRP for enhancing its bioavailability and targeting to brain for cluster headache (CH) treatment as an off-label use. Factorial design was conducted to analyze the impact of different components on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and percent drug release. Various in-vitro characterizations were performed followed by pharmacokinetic and brain targeting studies. The results revealed the significant impact of glyceryl monooleate (GMO) on increasing EE%, PS, and ZP of cubosomes with a negative influence on VRP release. The remarkable effect of Poloxamer 407 (P407) on decreasing EE%, PS, and ZP of cubosomes was observed besides its influence on accelerating VRP release%. The DSC thermograms indicated the successful entrapment of the amorphous state of VRP inside the cubosomes. The design suggested an optimized formulation containing GMO (50% w/w) and P407 (5.5% w/w). Such formulation showed a significant increase in drug permeation through nasal mucosa with high Er value (2.26) when compared to VRP solution. Also, the histopathological study revealed the safety of the utilized components used in the cubosomes preparation. There was a significant enhancement in the VRP bioavailability when loaded in cubosomes owing to its sustained release favored by its direct transport to brain. The I.N optimized formulation had greater BTE% and DTP% at 183.53% and 90.19%, respectively in comparison of 41.80% and 59% for the I.N VRP solution.Graphical

Preparation of silymarin-loaded zein polysaccharide core–shell nanostructures and evaluation of their biological potentials

Abstract Silymarin-loaded zein polysaccharide core–shell nanoparticles (SZPCS-NPs) were synthesized where sodium alginate and pectin offer stability and controlled release qualities to zein, a maize protein, having excellent biocompatibility. The present study is an attempt to develop zein–silymarin polysaccharide core–shell nanostructures to enhance water solubility, thereby improving bioavailability and producing enhanced biological responses in living systems. SZPCS-NPs were prepared using pH-induced antisolvent precipitation method. Five different types of SZPCS-NPs were synthesized using different combinations of sodium alginate and pectin, namely P100–A00 (non-uniform size ranging from 20 to 100 nm), P70–A30 (spherical and uniform size measuring approximately 80 nm in diameter), P50–A50, P30–A70, and P00–A100 exhibited irregular shapes with the presence of some triangular and oval structures and non-uniform size ranging from 20 to 100 nm. The SZPCS-NPs P70–A30 possessed the best results in terms of shape, size, and other characterization studies. Furthermore, the SZPCS-NPs possessed a percent drug loading of 72.5% and entrapment efficiency of 51.7%, respectively. The resulting SZPCS-NPs exhibited an excellent relative bioavailability percentage of 97.4% in comparison to commercial silymarin, having 58.1%, and crude silymarin, having 46.97% bioavailability percentage, correspondingly. In addition, SZPCS-NPs possessed an almost two folds’ increase in antioxidant activity in comparison to crude and commercially available silymarin. Similarly, SZPCS-NPs also showed better stabilization in hepatic biomarker enzymes and possessed better hepatoprotective activity for a period of 6 weeks, in contrast to commercial and crude silymarin formulations.

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.