Hydroxyl Propyl Methyl Cellulose Research Articles

Formulation, validation and evaluation studies on metaxalone and diclofenac potassium topical gel.

Twenty different batches of gels containing metaxalone and diclofenac potassium were prepared for topical application. These drugs act synergistically in the management of pain and inflammation. Gels were prepared by varying the type of gelling agent (ten batches each of hydroxyl propyl methyl cellulose and carbopol 934). The prepared gels were characterized and evaluated. Batch F7 emerged as the best batch on the basis of favourable pH, high drug content, homogeneity and drug release. HPLC (High-performance liquid chromatography) method validation of gel formulation was also carried out and the developed and validated method was found to be robust and accurate.

Comparison of the Properties of Egg Coating Materials Formulated by Blending Cassava Starch with Methyl Celluloses and Waxes and Their Effects on Egg Quality

An egg coating material was developed by blending cassava starch (CS) with gelling agents and wax. Hydroxyl propyl methyl cellulose and carboxymethyl cellulose (CMC) were added. Two waxes, beeswax and paraffin wax, were selected. CS blended with low-molecular-weight paraffin (Paraffin(L)) and CMC coating material displayed a tensile strength of 4 MPa, 34% elongation at break, 0.0039 g day−1 m−2 water vapor permeability, and a water contact angle of 89° at 3 min. Eggs coated with CS/CMC/Paraffin(L) solutions had a Haugh unit value of 72 (AA grade) and exhibited a weight loss of 2.4% in 4 weeks. CMC improved the compatibility of CS and Paraffin(L). This improvement and the hydrophobicity of Paraffin(L) conferred suitable mechanical and water-resistance properties on the coating material to maintain the quality of the coated eggs at AA grade with low weight loss for 4 weeks.

Formulation optimization and characterization of transdermal film of curcumin by response surface methodology

ObjectiveIndia is referred as goldmine of herbal drugs but still lack of optimization of herbal drugs, which has kept us on the back foot. The rationale of the study is to prepare optimized transdermal drug delivery system of curcumin employing response surface methodology to study the collective effect of independent variables like concentration of ethyl cellulose, hydroxyl propyl methyl cellulose and dibutyl phthalate which significantly influenced characteristics like percentage elongation and in vitro drug release. MethodTwenty formulations containing varying concentrations of polymers and permeation enhancer were prepared using solvent casting technique. ResultThe study revealed that the effect of dibutyl phthalate (DBP) concentration was the highest on percentage elongation (P < 0.0001), while hydroxy propyl methyl cellulose (HPMC) concentration exhibited pronounced effect on drug release (P < 0.0001) through dialysis membrane. Linear model fitted the best for curcumin release and elongation for all formulations. According to Derringer’s desirability prediction tool, the composition of optimized film was found to be 242.14% of HPMC, 109.59% of ethyl cellulose (EC), and 1.03% of DBP. Under these conditions, the optimized patch exhibited a predicted value of %elongation and in vitro drug release of 94.35% and 80.0306%, respectively, which was comparable to the actual values of percent elongation and in vitro drug release i.e. 95.02% and 81.03% respectively. FTIR and thermal studies were also performed which revealed no interaction or complexation between drug and excipients. The ex vivo study performed using rat skin showed that the cumulative drug release from the optimized patch showed flux of (30.68 ± 18) µg/cm2/h. ConclusionIt can be concluded that in future if proper optimization of herbal formulations is carried out, they can become the first choice for patients as compare to synthetic drugs.

Valsartan solid lipid nanoparticles integrated hydrogel: A challenging repurposed use in the treatment of diabetic foot ulcer, in-vitro/in-vivo experimental study

The article presents an experimental study on the possible repurposed use of valsartan (Val), in the local treatment of uncontrolled diabetic foot ulcer. Solid lipid nanoparticles (SLN), loaded with Val were prepared by applying 32 full factorial design using modified high shear homogenization method. The lipid phase composed of Precirol® ATO 5 (P ATO 5) and/or Gelucire 50/13 (G 50/13) in different ratios and a nonionic emulsifier, Pluronic 188 (P188), was used in different percentages. Optimized formulation was further integrated in hydroxyl propyl methyl cellulose (HPMC) gel for the ease of administration. In-vitro and in-vivo characterizations were investigated. The prepared nanoparticles showed small particle size, high entrapment efficiency and sustained drug release. Microbiologically, Val-SLN showed a prominent decrease in the biofilm mass formation for both gram-positive and gram-negative bacteria, as well as a comparable minimum inhibitory concentration level to levofloxacin alone. Diabetes was induced in 32 neonatal Sprague-Dawley rats. At 8 weeks of age, rats with blood sugar level >160 were subjected to surgically induced ulcer. Treatment with Val-SLN for 12 days revealed enhanced healing characteristics through cyclooxygenase-2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nitric oxide (NO), transforming growth factor-beta (TGF-β), matrix metalloproteinase (MMPs) and vascular endothelial growth factor (VEGF) pathways. Histological examination revealed re-epithelization in Val-SLN treated ulcer, as well as decrease in collagen using trichrome histomorphometric analysis.

Formulation of Piperine Ternary Inclusion Complex Using β CD and HPMC: Physicochemical Characterization, Molecular Docking, and Antimicrobial Testing

The present study was designed to evaluate the effect of hydroxyl propyl methyl cellulose (HPMC) on the complexation efficiency and dissolution of piperine (PPR) and β cyclodextrin (β CD) complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and microwave irradiation methods. The samples were further evaluated for physicochemical evaluation, morphology, antimicrobial, and antioxidant activities. The binary and ternary samples showed high stability constant (Ks) value and complexation efficiency (CE). The dissolution study results revealed marked enhancement in the release of the binary inclusion complex and ternary inclusion complex compared to pure PPR. Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), and molecular docking results confirm the complex formation. X-ray powder diffractometry (XRD) and scanning electron microscopy (SEM) data revealed modification in the structure of PPR. 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and antimicrobial results showed enhanced activity in the PPR complex in comparison to pure PPR. In conclusion, a remarkable enhancement in dissolution, antioxidant and antimicrobial activities were attained due to marked improvement in solubility through complexation of PPR with HPMC/β CD.

The Formulation and Evaluation of Gastro-Bilayer Floating Tablets of Losartan Potassium as Immediate Release Layer and Ramipril Hydrochloride as Sustained Release Floating Layer

Objectives: A sustained release Gastro-bilayer floating tablets with reduced dosing frequency and increased drug bioavailability is developed. The dosage form is suitable for the release of two drugs simultaneously in a single dosage unit i.e. Losartan Potassium and Ramipril Hydrochloride. The SeDeM system for selection of powder blend for direct compression gave the parameter index value of ≥0.5 which is considered as best in terms of compression properties. The prepared dosage form provided sustained effect of the drug for 12 hr by Non-Fickian, controlled diffusion and swollen matrix. Peppa’s release model is best suited for the final formulation of batches. Optimized formulation exhibited floating time of 12 hr and floating lag time of less than 1 min. In-vitro dissolution studies shows 96% of the both the drugs release. The swelling and erosion of polymers is studied by Scanning Electron Microscopy. The data obtained from Analysis of variance demonstrated the significance of the model with a P-value of less than 0.05. Methods: SeDeM system was adopted on powder blend before direct compression for preparation of tablet, the hydroxyl propyl methyl cellulose was used as a rate-controlling polymer and a mixture of citric acid and Sodium bicarbonate formed the floating layer. Results: Radius values through SeDeM diagram was plotted and index values are calculated and resulted in an index value of ≥0.5. The pre-compression and post compressional parameters are as per Indian Pharmacopeia specifications. The best formulation for gastric bilayer tablet had a combination of Hydroxy propyl methyl cellulose K15M and Sodium Carboxy methyl cellulose which gave 99.57% drug dissolution within 12 hr. Conclusion: Gastro-Bilayer Floating Tablets of Losartan as Immediate Release layer and Ramipril as sustained-release floating layer are successfully developed. The problem of poor solubility of drugs can be solved by optimization of blend through SeDeM expert System. Hydroxy propyl methyl cellulose K15M, K4M and Carbopol 934 are helpful in achieving the sustained effect of the drug for 12 hr by Non-Fickian, controlled diffusion and swollen matrix. Peppa’s release model is best suited for the final formulation batches based on the drug release mechanisms.

Drug release from hydrogel-based matrix systems partially coated: experiments and modeling

Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics.

In vitro characterization of mucoadhesive polysaccharide polymers tablets fabricated using FTIR press

Background and Aim: Buccal/sublingual drug delivery is gradually becoming one of the most experimented routes for alternate drug delivery. The major advantage of both routes is their high vascularity that allows a substantial permeation of drugs into systemic circulation. Mucoadhesive biopolymers are the mainstay of a transmucosal drug delivery system. Methods: We formulated blank tablets of explored mucoadhesive biopolymers (sodium alginate, carboxymethyl cellulose, hydroxyl propyl methyl) cellulose using a combination of two at a time. The novelty of this script lies in the formation of tablets using the FTIR hydraulic press, as opposed toa conventional tablet punching machine, at two different pressures. The tablets were subjected to basic characterizations of polymeric interaction, hardness, and swelling behaviour. Results: An interaction analysis using XRD revealed a good interaction between the polymers. HC-300 and AC-300 were found to be the hardest among the tablets formulated. In terms of swelling behaviour, AC-200 and HA-300 displayed the best swelling as compared to other combinations. Conclusion: In the absence of a conventional tablet punching machine, we fabricated swellable biopolymeric tablets using the regular KBr hydraulic press that comes as an accessory with the FTIR instrument. These tablets can possible be used for delivering drugs through buccal mucosa.

Pharmacodynamics and pharmacokinetics behaviour of insulin from PEGylated-mucin microparticles coated with pH sensitive polymer: Preparation and characterization

The aim of this study was to develop a mucin-PEG based microparticles for oral delivery system for insulin for diabetes treatment. Mucin-PEG microparticles were prepared using emulsion technique. These microparticles were coated with Hydroxyl propyl methylcellulose acetate succinate (HPMCAS) using solvent evaporation method. The effect of polymer ratios and coating were investigated in terms of size, surface morphology, entrapment efficiency, micrometrics properties, in vitro release and in vivo studies. The size of insulin-loaded MPs is > 80 μm and exhibited rough surface with irregular shape. The maximum and minimum encapsulation efficiency were 89.10 and 75.15 %, respectively. In vitro release study in pH 1.2 revealed insignificantly low (6 %) (p < 0.05) as compared to the significantly high (85 %) released obtained in pH of 7.4 for formulation combined PEG/mucin ratios (batches B1, B2 and B3). Furthermore, in vivo experiments in Wistar Albino rat model demonstrate that insulin-loaded MPs effectively reduced blood glucose levels over a period of 10 h after oral administration. Therefore, these findings clearly suggest that the HPMCP-coated PEG-mucin microparticles offer an interesting mode of insulin delivery orally for the treatment of diabetes.

Preparation of the Dermal Mucoadhesive Film Containing Mupirocin

Direct drug delivery of the antibiotics to the site of infection has many advantages such as reducing the adverse effect and achieving the minimum inhibitory concentration in the infected tissue. The goal of the study is to formulate the skin patch containing mupirocin as the antibiotic for the local drug delivery to the skin lesions such as burning ulcers on the surface of the skin. The different skin patches with the different polymers as the film former were applied for formulating the patches containing 2% mupirocin as the antibiotics. The patches were fabricated by the different ratio of chitosan, hydroxyl propyl methyl cellulose (HPMC) and polyethylene glycol (PEG) as the film former. The important characteristics of each film such as antibacterial activity, mucoadhesive properties and the release rate of mupirocin from the patches were measured by the in vitro tests. The suitable formulations were selected for the animal test. The results of the in vitro tests showed that the type of the polymer which were applied for the fabrication of the films and the chitosan to HPMC ratio in the structure of the films are the important effective factor on the characteristics of the films such as antibacterial activity and mucoadhesive properties of the patches. Increasing the percentage of the HPMC and chitosan in the structure of the patches caused to increase the mucoadhesive properties of the films. The antibacterial activity for the patches which were fabricated by HPMC as the film former was more than the others. More than 50% of drug was released from the films during 2 hours in all the formulations. Application of chitosan in the structure of the films caused to decrease the release rate of mupirocin from the films. The results of the in vivo tests showed that the most suitable efficacy belonged to the slow release formulations [1-5].

Effect of Particle Size and Viscosity of Suspensions on Topical Ocular Bioavailability of Budesonide, a Corticosteroid.

Purpose: To determine the effect of particle size and viscosity of suspensions on topical ocular bioavailability of budesonide, a corticosteroid drug. Methods: Budesonide microparticle and nanoparticle (MP and NP) suspensions were prepared with or without homogenization and microfluidization. Using different grades of hydroxyl propyl methyl cellulose, low viscosity NP (NP-LV) and low and high viscosity MP (MP-LV and MP-HV) were prepared. Suspensions were characterized for particle size, viscosity, and osmolality. Budesonide suspensions were administered topically to rabbits and aqueous humor was collected and analyzed for budesonide. Budesonide Cmax, tmax, and the area under the concentration time curve (AUC (0-6h)) values were determined. The geometric mean ratio of AUC and bioequivalence was evaluated using a bootstrap method. Results: The particle sizes for NP and MP were ∼700 and 2,000 nm. The viscosities for low and HV formulations were ∼5 and 50 cP. The geometric mean budesonide Cmax values for the suspensions NP-LV, MP-LV, and MP-HV were 0.22, 0.22, and 0.31 μg/g, tmax values were 0.67, 0.60 and 0.53 h, and AUC0-6h values were 0.72, 0.53, and 0.95 μg h/g, respectively. Bootstrap analysis indicated that the 90% confidence intervals of the geometric mean ratio of AUC0-6h values were 1.00-1.74 (MP-HV vs. NP-LV), 0.57-0.96 (MP-LV vs. NP-LV), and 0.45-0.70 (MP-LV vs. MP-HV). Conclusions: The 3 budesonide suspensions assessed in this study were not bioequivalent. Results suggested that an increase in viscosity improves the bioavailability of budesonide from the microsuspension formulation.

Comprehensive review of the role of acrylic acid derivative polymers in floating drug delivery system.

In the development of drug delivery systems, an oral drug delivery system is the preferred route of drug administration. Many components play an important role in developing a drug delivery system. Amongst those components, polymers have evolved with these systems. Macromolecule compounds consisting of many monomer units which are joined to each other by different bonds are known as polymers. For drugs that are absorbed primarily in the upper gastrointestinal tract, floating drug delivery systems offer an additional advantage. The purpose behind this review was to focus on different types of floating drug delivery systems and different types of polymers used in floating drug delivery systems, focusing on acrylic acid derivatives and their applications. In this review, the main emphasis is on acrylic acid derivative polymers, their formulation and grades, and various patents on these types of polymers. Based on the literature survey, mainly 2 types of polymers are used in this drug delivery system; i.e., natural and synthetic. Examples of natural polymers are xanthan gum, guar gum or chitosan, and synthetic polymers include acrylic acid derivatives and hydroxylpropyl methylcellulose (HPMC). Eudragit and Carbopol are the most widely used acrylic acid derivatives.

Facile fabrication of silk fibroin microparticles: their characterization and potential adsorption study

Silk fibroin (SF) microparticles were fabricated by blending of SF solution with hydroxyl propyl methyl cellulose (HPMC), and the SF/HPMC blend films were prepared using simple solvent evaporation technique. The SF/HPMC blends were dissolved in ultrapure water, and SF microparticles were generated with and without sonication. Fourier transformation infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA)/derivative thermogravimetric (DTG) measurements were used for the characterization of blend films and microparticles. The microparticles obtained sonicated consist of nanosized pores on the surface. The size of the pores was nano, but the diameter of particles was around 10 µm. Further, SF microparticles were evaluated as a novel biosorbent for the methylene blue (MB), a cationic dye. The influential factors (pH, contact time) to the adsorption of the dye by the microparticles were investigated. The SF microparticles showed a very good adsorption capacity of about 490 (nonsonicated) and of about 512 (sonicated) mg/g of the dye without any surfactants. The adsorption kinetics validates the practicality of using the pseudo-second-order kinetics. Langmuir and Freundlich isothermal models were used, and the results showed that the adsorption behavior of the samples best fits (R2=0.998) the Langmuir model. The easy preparation and obtained results suggest that the SF microparticles can be used as effective adsorbent for MB dye removal.

A study on the impact of HPMC viscosity grade and proportion on the functional properties of co-freeze-dried mannitol-HPMC cushioning excipients for compacted MUPS

The co-processing of multiple excipients is driven by the potential of diversifying the properties and functionality of excipients when they are combined. Bulk freeze-drying-milling is a novel secondary processing approach to develop co-processed excipients. It offers a significant advantage of formulation flexibility. This study was designed to systematically investigate the impact of 3 factors, hydroxylpropyl methyl cellulose (HPMC) viscosity grade, mannitol to HPMC ratio and particle size fraction on the functional properties of freeze-dried (FD) mannitol-HPMC cushioning excipients produced for multi-unit pellet system tableting. Based on the results, the investigated formulation variables were significant in determining the functional properties of the FD-mannitol-HPMC cushioning excipients. Among the formulations, FD-mannitol-HPMC F4M (3:1 ratio) excipients exhibited the best cushioning performance. It was postulated that the protective effects of the cushioning excipient were brought about by its propensity for rearrangement around the coated pellets to reduce detrimental pellet-pellet contact and ability to absorb damaging compressive forces. Conversely, FD-mannitol-HPMC vLV (3:1 ratio) had cushioning effects but showed short disintegration time while maintaining adequate tablet tensile strength. Overall, the results of this study highlighted the impact of formulation variables on the functional properties of the cushioning excipients, arising from an interplay of the freeze-dried particle properties.

Preparation and Evaluation of Sulfacetamide Sodium Ocusert for Controlled Drug Delivery

The intent of this research was to formulate and evaluate controlled release ocusert of sulfacetamide sodium for the treatment of bacterial conjunctivitis. Ocusert is a sterile preparation having drug as dispersion or as solution in the polymeric base. Prepared Ocuserts were formulated using hydroxyl propyl methyl cellulose K-15 and Ethyl cellulose as polymers at various concentrations and combinations. Polymeric Films were prepared by mercury casting method using different ratios of polymers. Selected physiochemical properties such as thickness, weight, percentage moisture absorption, and in-vitro release and sterility studies of sulfacetamide sodium ocusert were studied and reported that prepared ocusert resolved the problems of poor bioavailability, frequent dosing and wastage of active ingredient.&#x0D; Keywords: Hydroxypropyl methyl cellulose K-15, ocusert, sulfacetamide sodium

Endothelial Safety and Efficacy of Ex Vivo Collagen Cross-linking of Human Corneal Transplants

To assess endothelial safety and efficacy of exvivo corneal collagen cross-linking (CXL) in human corneal transplants stored in 2 different culture media. Fellow-eye controlled laboratory study of exvivo human donor corneas. Three sets of paired human donor corneas, 5 pairs each, were stored in organ culture medium before deswelling either at 31 C or at room temperature. One eye of each pair was cross-linked by 0.1% riboflavin in hydroxylpropyl methylcellulose (HPMC) instillation for 10minutes followed by 10minutes of ultraviolet-A (9 mW/cm2) irradiation while contralateral eyes served as controls. In Set 1, endothelial cell densities were determined. In Set 2, paired samples were assigned to the 2 deswelling media and CXL efficacy was assessed comparing to untreated controls using collagenase-A-assisted enzymatic digestion. In Set 3, biomechanical testing was performed in the eye pairs (treated vs control) by stress/strain measurements. There was no difference in endothelial cell counts between CXL samples and controls (P= .21). No statistically significant difference in digestion dynamics was found between tissues stored in the 2 different culture media. Complete enzymatic digestion was slowed down by 3 hours in the cross-linked samples (P= .036). Stress needed for a 12% strain was increased by 34% in the treatment group compared to control (P= .04). Exvivo CXL of human donor tissue is an effective and safe procedure with no difference regarding efficacy between 2 commercially available deswelling media. Biochemical and biomechanical resistance were significantly increased after CXL. Patients requiring keratoplasty owing to corneal melting might benefit from the strengthening effect of preoperative CXL of donor tissue.

Formulation and Evaluation of Carbamazepine Tablets using Biosurfactant in Ternary Solid Dispersion System

Abstract: Objectives: The present study is aimed to develop and evaluate Carbamazepine tablets using ternary solid dispersed product. Carbamazepine belongs to BCS class II having low solubility. Ternary system was formulated with biosurfactant and water-soluble polymers to enhance dissolution rate and bioavailability. Methods: Binary and ternary solid dispersion was prepared using hydroxyl propyl methyl cellulose (HPMC) K-100, Polyvinyl pyrolidine (PVP) K-30 and Poly ethylene glycol (PEG) 6000 as a polymer and biosurfactant respectively by solvent evaporation method and evaluated for drug content uniformity and in-vitro dissolution study. Carbamazepine tablet were prepared by incorporation of ternary solid dispersed product along with other excipients by direct compression technique. Prepared formulations were evaluated for pre-compression and post-compression parameters. Oral toxicity study of biosurfactant was performed using female wistar rats. Results: In-vitro dissolution profile of optimized tablet formulation OF1 and OF2 showed 75.14% and 71.26% release in 1.2 pH respectively and similarly at 6.8 pH buffer 64.33% and 58.96% respectively. Pre-compression and postcompression values of formulated tablets were within the specified acceptable limits. In-vivo dissolution study of optimized formulation OF1 showed an increase in dissolution rate in accordance with pure drug. Oral toxicity study of biosurfactant was safe at 2000 mg per kg body weight of rat. Short term stability of the optimized formulation was stable without deviations at room temperature. Conclusion: Addition of biosurfactant in ternary solid dispersion system proved to be promising excipient in formulation of carbamazepine tablet for enhanced dissolution rate, dose reduction and bioavailability. Key words: Carbamazepine, Solid dispersion, Ternary system, Biosurfactant, in-vivo oral toxicity.

Evaluation of potential environmental toxicity of polymeric nanomaterials and surfactants

Nanomaterials have gained huge importance in various fields including nanomedicine. Nanoformulations of drugs and nanocarriers are used to increase pharmaceutical potency. However, it was seen that polymeric nanomaterials can cause negative effects. Thus, it is essential to identify nanomaterials with the least adverse effects on aquatic organisms. To determine the toxicity of polymeric nanomaterials, we investigated the effects of poly(lactic-co-glycolid) acid (PLGA), Eudragit® E 100 and hydroxylpropyl methylcellulose phthalate (HPMCP) on zebrafish embryos using the fish embryo toxicity test (FET). Furthermore, we studied Cremophor® RH40, Cremophor® A25, Pluronic® F127 and Pluronic® F68 applied in the generation of nanoformulations to identify the surfactant with minimal toxic impact. The order of ecotoxicty was HPMCP < PLGA < Eudragit® E100 and Pluronic® F68 < Pluronic® F127 < Cremophor® RH40 < Cremophor® A25. In summary, HPMCP and Pluronic® F68 displayed the least toxic impact, thus suggesting adequate environmental compatibility for the generation of nanomedicines.

English

Solid dispersion technique was successfully used to enhance the dissolution of poorly aqueous soluble drugs aceclofenac. Four carriers Hydroxyl propyl methylcellulose (HPMC), polyvinyl alcohol (PVA), Mannitol and Dextrose in two ratios (1:2, 1:3 w/w) were used to prepare solid dispersion. Eight different formulations were designed by the varying carrier and the drug: Carrier ratio and solvent wetting method was used for preparing solid dispersion. Acquired formulations were used for various micrometric and in vitro drug release studies. The solubility of aceclofenac in distilled water was 0.0753±0.021 mg/ml. The study shows that aceclofenac solubility is pH-dependent where the solubility observed was greater in phosphate buffer (pH 7.4) at 5.76±1.23 mg/ml compared to acid buffer (0.1 N HCl) at 0.0214±0.012 mg/ml. The percentage yield measured in F5 was higher at 85.18±6.02% and lower at 70.43±5.028% in F1. Micrometric study suggest that the Carr’s index and Hausner's ratio value was smallest for F4 with 5.018±0.0025 and 1.06±0.0025 respectively, indicating an excellent flow property and greatest for F6 with 15.35±0.0022 and 1.18±0.0022, indicating relatively poor flow. The angle of repose value was lower for F5 with 20.77±2.9o and higher for F2 with 30.77±2.1o. Both acid buffer (pH 1.2) and phosphate buffer (pH 7.4) were undertaken for in vitro drug release study of pure drug aceclofenac and eight separate formulations. The in vitro drug release after 180 min for aceclofenac in acidic buffer (pH 1.2) was 3.89±0.41% and was highest in F8 with 54.73±4.60 % and lowest in F5 with 31.75±3.10 %. Drug release was significant compared to pure drug aceclofenac (p<0.05) in acidic buffer. Similarly, in vitro drug release after 180 min for aceclofenac in phosphate buffer (pH 7.4) was 23.79±2.20% and was highest in F8 with 76.65±6.50% and lowest in F5 with 64.09±5.70%. The data was analyzed by Dunnett’s multiple comparison tests while statistical significance was predefined at p<0.05. Key words: Aceclofenac, hydroxyl propyl methylcellulose (HPMC), polyvinyl alcohol (PVA)

Carboxymethyl cellulose-based wafer enriched with resveratrol-loaded nanoparticles for enhanced wound healing.

The present study aimed to prepare and investigate the wound healing potential of carboxymethyl cellulose (CMC)-based wafers incorporated with resveratrol (RSV)-loaded cellulose acetate butyrate (CAB) NPs. Accordingly, RSV-CAB NPs were prepared using the solvent evaporation method. The effect of different formulation parameters (polymer content, surfactant concentration, and the volume ratio of aqueous phase to organic phase) on the properties of NPs was investigated using the Box-Behnken design. Then, the optimized NPs were incorporated in wafers comprising CMC combined with hydroxyl propyl methyl cellulose (HPMC) or chitosan. Hydration capacity, porosity, adhesive strength, and hardness of the prepared nanocomposite wafers were examined. Optimized formulation was spherical, showing the particle size, polydispersity index, zeta potential, encapsulation efficiency %, drug loading %, and release efficiency % of 248.5nm, 0.38, - 1.59, 87.58, 25.94, and 67.10, respectively. The CMC-HPMC wafers exhibited higher porosity, hydration capacity, and adhesive performance, as compared with the CMC wafers alone and CMC-chitosan wafers. Wound healing test and histological evaluation in the excisional wounds of the rats showed that the RSV-NPs-wafers were more effective as a healing accelerator, in comparison to wafers without drug or those containing the free RSV. These results demonstrated the potential of the RSV-NPs-wafer in wound healing drug delivery applications. Graphical abstract.