Carmellose Sodium Research Articles

OPTIMIZATION AND CHARACTERIZATION OF FAST DISSOLVING TABLETS OF CANDESARTAN CILEXETIL PREPARED FROM SPHERICAL AGGLOMERATES

The primary objective of this study was to develop a rapidly dissolving tablet containing an antihypertensive drug, candesartan cilexetil (CAND). The research work focused on improving solubility and in vitro dissolution of drugs using spherical agglomeration technique. Spherical agglomerates of CAND were developed using PVPK-30 as polymer and dichloromethane as bridging liquid. A spherical agglomerate of CAND was used to formulate fast dissolving tablet (FDT) with different superdisintegrants like Crospovidone and Cross carmellose sodium. The prepared powder blend was evaluated for different pre-compression parameters like solubility, compressibility index, Hausner’s ratio and flow property and post-compression parameters including in vitro dissolution study. The solubility of prepared agglomerates was found to be 0.15 to 0.91 mg mL-1, and it was higher than the pure drug (0.00071 mg mL-1). In vitro drug release study of optimized batch of FDT has shown 95.47 % of drug release. From the results, it was revealed that the prepared FDT using the agglomeration technique might be used to enhance the solubility and bioavailability of CAND to augment acute and chronic hypertension therapy.

Veterinary compounding: the impact of different gelling agents on the rheological characteristics and release kinetics from meloxicam oral gels in the treatment of cats

Worldwide, the growing number of pets has increased the use of veterinary drugs, as well as individualised therapy such as compounded drugs. If a suitable formulation or drug is not registered for veterinary species, drugs are compounded. This also includes pharmaceutical forms which are easy to administer, such as semi-solid preparations (gels and pastes) for oral use in order to enhance drug administration and adherence. The number of non-steroidal drugs (NSAIDs) approved for use in cats is relatively small. NSAIDs represent the largest group of drugs with adverse drug experience, but meloxicam has advantages in relation to all of them because of its safety for use in cats. In this study, the pharmaceutical-technological characterisation of oral gels for cats made with different gelling agents (carbomer, xanthan gum, carmellose sodium and hypromellose) was undertaken. Subsequently, four different samples were prepared and designed for veterinary use (using meloxicam, gelling agents and taste enhancer), and then the pH value, rheological characterisation and drug release were determined. The results demonstrated that addition of the taste enhancer influenced the rheological properties of the tested oral gels. It was found that the rate of meloxicam release was the highest from the oral gel prepared with carbomer (Carbopol® 974P), where complete meloxicam dissolution was observed after 5 minutes. On the basis of these results, it was concluded that Carbopol 974P has a certain advantage over the other gelling agents used in this study. Further work is required to assess the palatability of the oral gel for cats in clinical settings.

Fabrication and characterization of the novel tubular ceramic membrane using walnut shells and its application in TiO2 nanoparticles separation from suspension

Low-cost ceramic membranes have become highly popular in water treatment and gas separation industries. This study focuses on creating an affordable yet efficient ceramic membrane for effective separation processes. The cost-effective fabrication process combines locally sourced raw materials with optimal manufacturing techniques, resulting in minimal production expenses. To create this unique, low-cost ceramic membrane, a mixture of kaolin, quartz, and additives like zirconia and dolomite is used in shaping and sintering procedures. Walnut shell powder serves as a pore-forming agent, while carmellose sodium acts as a membrane-binding agent. The membrane is prepared through extrusion with dimensions of 110 mm in length and 12 mm in diameter, and it is sintered at temperatures of 850 °C, 900 °C, and 950 °C. Various analytical methods, including FESEM, XRD, and TGA, are employed for comprehensive characterization. The water flux increased with increasing pressure (54–215 kPa), and the pore diameter obtained from the test was consistent with the pore size obtained from FESEM. The membranes' pore size increases with higher sintering temperatures while porosity decreases. The membrane demonstrates mechanical strength, chemical stability, and high rejection efficiency in TiO2 separation. The total cost of one tubular membrane comes out to be $112 per square meter.

Tear Film Stabilization and Symptom Improvement in Dry Eye Disease: The Role of Hyaluronic Acid and Trehalose Eyedrops versus Carmellose Sodium.

This study evaluated the effectiveness of hyaluronic acid and trehalose (HA/trehalose) eyedrops in managing dry eye disease (DED) symptoms by measuring tear stability and administering a DED questionnaire. Sixty patients were treated with either HA/trehalose eyedrops (Tear A) or carmellose sodium eyedrops (Tear B) as controls. The tear breakup time (TBUT) and non-invasive breakup time (NIBUT) were monitored, and patients completed the standard patient evaluation of eye dryness (SPEED) questionnaire. After two months of twice-daily applications, patients treated with the HA/trehalose eyedrops demonstrated significant improvements in the NIBUT (12.98 ± 3.22 s) and TBUT (12.95 ± 2.98 s), indicating increased tear stability. Moreover, they reported lower dry eye sensation (6.70 ± 4.94 SPEED score points), suggesting a reduction in DED symptoms. These findings underscore the efficacy of HA/trehalose eyedrops in improving both the objective and subjective signs of DED, with twice-daily application enhancing ocular surface conditions and reducing patient-reported symptoms.

Immediate hypersensitivity reaction to carboxymethylcellulose in lidocaine jelly and dimethicone drops: A case report and mini‐review

AbstractExcipient allergies are rare and difficult to diagnose. Carboxymethylcellulose (CMC, carmellose sodium) is an anionic water‐soluble polymer derived from native cellulose, that is, used as an excipient. Here, we report a case of urticaria caused by the CMC in lidocaine jelly and dimethicone drops, which had used for upper gastrointestinal endoscopy. CMC is widely used in pharmaceutical preparations, food additives, and other pharmaceuticals, and its use is increasing. However, there are few reports on immediate hypersensitivity reactions because substances containing CMC. Previous reports and our case suggest that excipients, such as CMC, can be potential hidden allergens.

FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLETS OF ACECLOFENAC BY DIRECT COMPRESSION METHOD

Nowadays, Oro dispersible tablets are gaining much importance because it is easily approachable and due to its patient compliance. In this study, Formulation and evaluation of one such tablets of Aceclofenac by direct compression method using super disintegrants like Cross carmellose sodium (CCS) was performed.
 Due to low water soluble property of aceclofenac, it has poor dissolution and bioavailability. In order to minimize this property OTD’s are prepared. ODT’s were prepared by direct compression method using super disintegrant i.e Cross Carmellose Sodium (CCS) in different concentrations. The prepared powder blend was subjected to various evaluation studies like pre compression parameters like angle of repose, tapped density, and bulk density. Post compression parameters like weight variation, hardness, friability, drug content, wetting time, disintegration and dissolution studies were performed. The drug excipients compatibility was verified by FTIR.
 The precompression evaluation studies showed that the prepared powder blend has good flow property. The hardness and friability revealed that it has good mechanical strength with acceptable disintegration time. The optimized formulation indicated good in vitro drug dissolution profile with maximum drug being released at all the time intervals indicates an ideal profile for the development of ODT’s. The results of pre compression studies and post compression along with FTIR are presented.

Formulation and Assessment of Quick dissolving tablet of Candesartan cilexetil arranged from their circular agglomerates

Candesartan cilexetil is water insoluble drug which comes under BCS class second category. Drug was used in the treatment of acute and chronic hypertension. The research workgenerally focuses on the solubility enhancement, increasing dissolution behavior, flowability and compressibility of the drug. Tablets and capsule are the solid dosage form mostly used. Spherical agglomerates of Candesartan cilexetil were prepared. Candesartan cilexetil water insoluble drug was used. With the incorporation of polymer, Agglomerates of such drug was prepared. Fast dissolving tablet was prepared and evaluated. Evaluation parameter like FTIR, DSC was carried out. Precompression parameters like bulk density, tap density, angle of repose, compressibility index was carried out. Post compression parameters like friability, hardness, thickness, disintegration time, wetting time was carried out and evaluated. Effect of different disintegrant like Crospovidone, cross carmellose sodium was studied. From in vitro study it was found that cross carmellose sodium containing batch F3 shows better drug release so it shows enhanced dissolution rate while if cross carmellose sodium level increases thus decreasing their dissolution rate.

Influence of Bile Acids in Hydrogel Pharmaceutical Formulations on Dissolution Rate and Permeation of Clindamycin Hydrochloride

Clindamycin hydrochloride is a widely used antibiotic for topical use, but its main disadvantage is poor skin penetration. Therefore, new approaches in the development of clindamycin topical formulations are of great importance. We aimed to investigate the effects of the type of gelling agent (carbomer and sodium carmellose), and the type and concentration of bile acids as penetration enhancers (0.1% and 0.5% of cholic and deoxycholic acid), on clindamycin release rate and permeation in a cellulose membrane in vitro model. Eight clindamycin hydrogel formulations were prepared using a 23 full factorial design, and they were evaluated for physical appearance, pH, drug content, drug release, and permeability parameters. Although formulations with carbomer as the gelling agent exerted optimal sensory properties, carmellose sodium hydrogels had significantly higher release rates and permeation of clindamycin hydrochloride. The bile acid enhancement factors were higher in carbomer gels, and cholic acid exerted more pronounced permeation-enhancing effects. Since the differences in the permeation parameters of hydrogels containing cholic acid in different concentrations were insignificant, its addition in a lower concentration is more favorable. The hydrogel containing carmellose sodium as a gelling agent and 0.1% cholic acid as a penetration enhancer can be considered as the formulation of choice.

Optimization of diluents on the basis of SeDeM-ODT expert system for formulation development of ODTs of glimepiride

The present study aimed to optimize diluents characteristics (rheological characteristics, compressibility and disintegration behavior) using SeDeM-ODT expert system, to mask poor characteristics of APIs and will help in development of a formulation which is to be processed by direct compression technique. On the basis of SeDeM-ODT experts system, various parameters were determined for glimepiride, diluents and other excipients, and evaluated their suitability for direct compression and bucco-dispersibility. Diluents were selected and powder blend of all the developed formulations were tested as per SeDeM-ODT expert system. Powder blends were compressed to ODTs and cross carmellose sodium was used as super dissintegrant. Different parameters of the powder blend related to flow were evaluated while compressed tablets were subjected to various official and un-official quality control tests. SeDeM-ODT Experts system was successfully applied for optimization of diluents and all the formulations exhibited better flow, disintegration behavior and sufficient mechanical strength, irrespective of the addition of other excipients having poor characteristics. Results of the developed formulations was same as predicted in terms of rapid disintegration (disintegration < 60sec) and high mechanical strength (crushing strength greater than 40 N) of the tablets. SeDeM-ODT expert system can help in selection of diluents with optimum characteristics, required for tablet preparation by direct compression, facilitating the process of formulation development and avoided extensive experimentation, as carried out in conventional statistical optimization.

The effect of biomaterials of cross carmellose sodium and Eudragit S-100 as model polymers on colon targeted drug release in different dosage forms

The aim of this study to find out the role of biomaterial cross carmellose sodium and Eudragit s100 is to control the drug release drug dosage form into a particular site, colon, which is part of large intestine. The drug Budesonide was used as a model drug. In this study nine formulations (F1-F9) were prepared using different concentration of polymer, cross carmellose Sodium and all were evaluated as per standard parameters, and found as per prescribed standards. All formulation were pursued for coating process using Eudragit S100 as a polymer and different excipients like castor oil act as a plasticizer, talc as anti-agglomerative agent. All the formulation showed significant role in gastric media, i.e. 0.1 NHCl does not release the drug in in GI fluids for 2 h. Most of the formulation has given their release above 90% but F4 has given its release 99.4 in 36 h in colon part of large intestine. It shows a sustained and constant release performance till next 36 h which showing the best release among all formulation.

Monitoring of Cocrystal Dissociation during the Wet Granulation Process in the Presence of Disintegrants by Using Low-Frequency Raman Spectroscopy.

The aim of this study was to evaluate the effect of three coformers and five disintegrants in the granulation formulation on the dissociation of cocrystal during the granulation process by monitoring wet granulation with probe-type low-frequency Raman (LF-Raman) spectroscopy. As model cocrystals, paracetamol (APAP)-oxalic acid (OXA), APAP-maleic acid (MLA), and APAP-trimethylglycine (TMG) were used. The monitoring of the granulation recipe containing cocrystals during wet granulation was performed over time with high-performance LF-Raman spectrometry and the dissociation rate was calculated from the results of multivariate analysis of LF-Raman spectra. The dissociation rate decreased in the order of APAP-TMG, APAP-OXA, and APAP-MLA, showing the same order as observed in Powder X-ray diffraction measurements. Furthermore, to compare the effect of disintegrants on the dissociation rate of APAP-OXA, LF-Raman monitoring was performed for the granulation recipes containing five typical disintegrants (two low-substitution hydroxypropyl cellulose (HPC), cornstarch (CSW), carmellose sodium (CMC), and crospovidone (CRP)). The dissociation rate of APAP-OXA decreased in the order of CSW, HPCs, CMC, and CRP. This difference in the dissociation rate of APAP-OXA was thought to be due to the disintegration mechanism of the disintegrants and the water absorption ratio, which was expected to affect the water behavior on the disintegrant surface during wet granulation. These results suggested that probe-type LF-Raman spectroscopy is useful to monitor the dissociation behavior of cocrystals during wet granulation and can compare the relative stability of cocrystal during wet granulation between different formulations.

Antibacterial and clusteroluminogenic hypromellose-graft-chitosan-based polyelectrolyte complex films with high functional flexibility for food packaging

Food packaging can extend the shelf life of food products and enhance the safety and quality of the food. This study reports food-grade polyelectrolyte complex films generated via electrostatic interactions between two cellulose-based agents [viz., hypromellose-graft-chitosan, and carmellose sodium]. At optimal conditions, our films show good barrier properties, high transparency, and high efficiency in post-production agent loading. They also demonstrate intrinsic antibacterial effects against both Gram-negative and Gram-positive bacteria. By using frozen chicken breasts as a model, the films enable real-time monitoring of the status of the frozen food due to the property of clusterisation-triggered emission. Along with their negligible toxicity, our films warrant further development as multi-functional films for effective and self-indicating food packaging.

FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF LANSOPRAZOLE BY SOLUBILITY ENHANCEMENT TECHNIQUE

The present study was focused on preparation and evaluation of Lanzoprazole fast dissolving tablets. Lansoprazole (LAN) is a proton pump inhibitor drug and used for the treatment of gastric ulcer. Lansoprazole is acid labile drug and to avoid the acidic pH of the stomach LAN is formulated as oral fast dissolving tablets. Lansoprazole is the class II drug of the BCS classification and has a low aqueous solubility. Hence, to improve the solubility of the drug we have prepared Lansoprazole solid dispersion with poly ethylene glycol and complex with β cyclodextrin. Fast Dissolving tablets of LAN were formulated using different superdisintegrants like Sodium Starch Glycolate, Cross Povidone, Cross Carmellose Sodium by direct compression method. The prepared fast dissolving tablets were evaluated for various parameters like weight variation, hardness, friability, disintegration time, drug content, wetting time, in-vitro drug release and short term stability studies. Percentage weight variation, hardness, friability and drug content uniformity were found to be within the approved range for all the formulations. The in-vitro release studies showed that 99.6% of LAN within 90 sec. Overall, in the formulations prepared by the direct compression method, F3, which contains 6% CCS as super disintegrants release 99% of (LAN) in 2 min was found to be the best formulation. The results concluded that fast dissolving tablets of LAN showing enhanced dissolution might lead to improved bioavailability and effective therapy for gastric ulcer. KEYWORDS: β cyclodextrin, Cross Povidone, Fast dissolving tablets, Gastric ulcer, Lanzoprazole, Solid dispersion

FORMULATION DEVELOPMENT AND EVALUATION OF CHRONOMODULATED DRUG DELIVERY SYSTEM BY ZAFIRLUKAST

Objective: The main objective of the present study was to formulate and evaluate a time-controlled single-unit oral pulsatile drug delivery system containing Zafirlukast for the prevention of nocturnal asthma attacks. To provide time-scheduled drug release for Asthma disease. It is used for preventing asthmatic attacks at early morning. Pulsatile release dosage form is increasing patient compliance by reducing the dosing frequency, especially in the early morning.&#x0D; Methods: Core tablets were prepared by incorporating different concentrations of natural and synthetic super disintegrants. Drug-containing core tablets (ZC1-ZC15) with different compositions of natural super disintegrants (Plantago ovata seed powder, Locust bean gum) synthetic super disintegrants (Sodium starch glycolate (SSG), Cross carmellose sodium (CCS), Crospovidone (CP)) were prepared by direct compression technique. The core tablets were subjected to pre-formulation, physicochemical and In vitro drug release studies. The fast disintegrating core tablet formulation was selected and press-coated tablets (P1-P11) were prepared with different compositions of hydrophobic polymers Eudragit RS100, Eudragit RL 100, Ethylcellulose and hydrophilic polymers Hydroxypropyl methylcellulose K4M, K100M. The optimized formulation was selected and quantified based on in vitro drug release profile in simulated gastric and intestinal fluids.&#x0D; Results: The pre and post-compression parameters of tablets were also found to be within limits. Formulation ZC5 with 16 mg of Locust bean gum showed the least disintegrating time, i.e., 22.13 sec, and was selected as the best immediate release core tablet. The press-coated tablet formulation P8 having 62.5 mg Eudragit RS100 and 62.5 mg of HPMC K4M in ratio 1:1 over the core tablet ZC5 showed rapid and drug release nearly after 4 h lag time and 98.86 % up to 12 h. Accelerated stability studies of the optimized formulation P8 indicated no significant difference in release profile after 3 mo.&#x0D; Conclusion: The in vitro dissolution study showed that lag time before drug release was highly affected by the coating amount level and nature of coating polymer used. Time-controlled pulsatile release tablets can be prepared using press-coating techniques.

DEVELOPMENT AND CHARACTERIZATION OF ORAL SWELLABLE RAPID RELEASE FILM WITH SUPERDISINTEGRANT-SURFACTANT

Objective: Oral disintegrating films consisting of hydrophilic polymer are designed to be quickly hydrated by saliva, adhere to the mucosa and disintegrate rapidly to release the drug. The aim of the present study was to prepare stable, flexible swellable rapid release oral films with hydroxypropyl methylcellulose E15 LV (HPMC) and polyvinyl alcohol (PVA) in different ratios. Guar gum was incorporated as the mucoadhesive agent. In order to achieve rapid disintegration of the film cross carmellose sodium (superdisintegrant) and surfactant like Tween 80 were added. The model drug used in the study was diclofenac sodium.&#x0D; Methods: Films were developed using HPMC E15 LV and PVA by solvent casting method and characterized for thickness, swelling index, disintegration time, folding endurance, drug content, and in vitro drug release pattern and kinetics.&#x0D; Results: The prepared swellable rapid release oral films were quite flexible and transparent with a smooth texture. The swelling index study confirmed that the films possessed the desired swelling property. Fastest disintegration was observed with the oral film containing HPMC: PVA in the ratio of 2:1, guar gum at 120 mg, 20% w/w crosscarmellose sodium and 4%w/w Tween 80. The swellable rapid release oral films were found to follow either Higuchi or Korsmeyer-Peppas model with drug release following either Fickian or non-Fickian diffusion. Maximum drug release of around 70% was observed from the above-mentioned film in 1hr in simulated salivary fluid.&#x0D; Conclusion: Therefore, swellable rapid release oral films with HPMC E15 LV: PVA, guar gum, croscarmellose sodium and Tween 80 demonstrated satisfactory swelling, rapid disintegration and improved drug release for oromucosal absorption.

INVENTORY DIGITAL MANAGEMENT USING STATISTICAL PROCESS CONTROL ANALYSIS IN HEALTHCARE INDUSTRY

Inventory management in the healthcare industry is of prime importance to ensure the appropriate delivery of the medical and health products to the final customer in a reasonable time without shortage or overstocking of the goods. The achievement of this balance, in turn, is dependent on the production of the product in a timely manner through dynamic control of the inventory mobility of the input materials in the warehouse. In the present study, eight raw materials, which are used as excipients in healthcare products, were selected as a focus research group for analysis using statistical process control (SPC: process-behavior (trending/control) charts, Pareto plots, Box plot diagrams and Pie illustrations), namely Macrogolglycerides, MCC, Sodium Benzoic Sulfimide, Carmellose Sodium, Isofol 20, Citric Acid Hydrate, Ace K and Sodium Hydrate. Inventory autonomous management network was integrated with SPC software (Minitab®v17.1.0) using the generated database. A unique and simple index was created to prioritize and evaluate each material quantitatively based on material mass, rejection factor, deliveries intervals and the lag time before disposition. Isofol 20 and MCC contributed by about 70% as a material risk weight (MRW). This index is useful for objective comparative analysis, measurement of the degree of changes quantitatively and decision-making.

Efficacy of 0.1% crosslinked hyaluronic acid, coenzyme Q10 and vitamin E in the management of dry eye disease in menopause patients receiving antidepressants.

The purpose of this study is to test non-inferiority of a lower dose of crosslinked hyaluronic acid (CLHA) to a higher dose of carmellose eye drop in menopause patients receiving antidepressant treatments. This prospective, double-blind, single-center study enrolled sixty female patients. Mean age was 63.25 ± 9.13 years. We examined patients with Schirmer I, breakup time (TBUT) and the ocular surface disease index (OSDI) at the first visit. Tear A eyedrops were formulated with crosslinked hyaluronic acid, coenzyme Q10 and vitamin E. Control tear B was formulated with carmellose sodium. Posology was two and five times, respectively. After 2 months of treatment, the tear A obtained 14.12 ± 7.47 score points for OSDI (t = 11.74, p < 0.01), and tear B obtained 19.46 ± 10.03 score points (t = 7.59, p < 0.01). The tear A obtained 13.77 ± 7.78 score points for Schirmer test (t = 0.88, p > 0.05), and tear B obtained 14.20 ± 8.62 score points (t = 2.92, p < 0.01). The tear A obtained 8.30 ± 2.08 s for TBUT (t = 15.50, p < 0.01), and tear B obtained 7.23 ± 2.40 s (t = 8.79, p < 0.01). Lower total daily dose of crosslinked hyaluronic acid eyedrops obtained similar efficacy results in terms of tear stability and subjective dry eye sensation than higher carmellose total daily dose. A lower total daily dose of crosslinked eyedrops was sufficient to achieve better dry eye disease management compared to carmellose.

Berberine Down-Regulated Myostatin Expression and Facilitated Metabolism via Smad Pathway in Insulin Resistant Mice.

ObjectiveTo explore the effect of berberine (BBR) on skeletal muscle mass and metabolism and the possible mechanism.MethodsEight-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 8 weeks to establish the insulin resistance obesity model. Then, mice were randomly divided into two groups (normal chow diet (NCD) and HFD), while NCD and HFD were further classified into two groups respectively, which were NCD+CS (Carmellose Sodium), NCD+BBR, HFD+CS and HFD+BBR. After the BBR intervention, insulin tolerance test (ITT) and glucose tolerance test (GTT) were carried out. Metabolic parameters and inflammatory biomarkers were detected. Various parts of adipose tissue and gastrocnemius were separated and measured. The gastrocnemius muscle was selected for tissue staining. The mRNA expression of myostatin (Mstn) was tested by quantitative real-time PCR (RT-PCR). Western blotting was performed to detect the expression of Mstn, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), small ribonucleoprotein particle protein 2 (Smd2), small ribonucleoprotein particle protein 3 (Smd3), and small ribonucleoprotein particle protein 4 (Smd4).ResultsBoth body weights (P<0.01) and various parts of fat mass (P<0.001) were decreased significantly, while muscle mass was increased in the HFD group after being treated with BBR. Meanwhile, the glucose and lipid metabolic disorders as well as inflammation status were improved. RT-PCR and Western blotting analysis showed that, after being fed with HFD the expression of Mstn mRNA and Mstn were significantly increased, and decreased after being treated with BBR. Western blotting analysis also showed that, compared with the NCD group, the expressions of Smad2, Smad3, and Smad4 were all increased in the HFD group, but after being treated with BBR, the expressions of Smad3 and Smad4 were decreased.ConclusionOur study revealed that BBR could improve metabolic disorders and inflammation status, decrease Mstn expression, and increase skeletal muscle mass, which was associated with the Smad pathway.

Percutaneous delivery of levetiracetam as an alternative to topical nonsteroidal anti-inflammatory drugs: formulation development, in vitro and in vivo characterization.

The study focused on formulation of carmellose sodium hydrogels and nonionic microemulsions with 5% and 10% of levetiracetam and investigation of drug concentration influence on their physicochemical characteristics and in-use stability as well as influence of drug concentration and carrier type on in vitro drug release and in vivo antihyperalgesic/antiedematous activity in a rat model of localized (intraplantar) carrageenan-induced inflammation. Hydrogels were pseudoplastic semisolids with thixotropy and pH 7.37-7.58. Microemulsions were low viscous Newtonian nanodispersions of oil droplets (13.11-15.11nm) in water, with pH 4.01-4.64. Physical stability of the investigated systems was preserved over the 3-month storage under ambient conditions. Levetiracetam release followed zero order and Korsmeyer-Peppas models (R2 ≥ 0.99) reflecting the combined effects of drug concentration and carrier viscosity. All levetiracetam-loaded formulations produced significant reduction of hyperalgesia and paw swelling induced by carrageenan (p < 0.001). Their efficacy in exerting antihyperalgesic activity was significantly higher than that observed with the reference 5% ibuprofen hydrogel preparation (up to 6h) (p < 0.001), while antiedematous activity was comparable with the reference product. No erythema and visible blood vessels were observed in a rat ear test. The study demonstrated percutaneous delivery of levetiracetam as useful and safe therapeutic option for localized inflammatory pain with potential to overcome the insufficient efficacy of topically applied nonsteroidal anti-inflammatory drugs in the form of a hydrogel. Graphical abstract.

Optimization and Quality by Design Approach for Piroxicam Fast Dissolving Tablet Formulations Using Box-Behnken Design

Background: The present study deals with the formulation and optimization of piroxicam fast dissolving tablets and analyzes the impact of an independent variable while selecting the optimized formulation utilizing Quality by Design (QbD) and Box-Behnken Design (BBD). Methods: Seventeen formulations were prepared by direct compression technique by altering the proportion of cross carmellose sodium, spray dried lactose and hydro propyl methyl cellulose (HPMC K4M). The BBD statistical technique was used to optimize formulations and correlate the relationship among all the variables. Also, the powder mixture characteristics and tablet physiochemical properties such as hardness, friability, drug content, Disintegration Time (DT) and dissolution test were determined using 900 ml of 0.1N HCl (pH-1.2) at 37 ± 0.5°C. Results: Significant quadratic model and second order polynomial equations were established using BBD. To find out the relationship between variables and responses, 3D response surface and 2D contour plot was plotted. A perturbation graph was also plotted to identify the deviation of the variables from the mean point. An optimized formula was prepared based on the predicted response and the resulting responses were observed to be close with the predicted value. Conclusion: The optimized formulation with the desired parameter and formulation with variables and responses can be obtained by BBD and could be used in the large experiment with the involvement of a large number of variables and responses.