“Extraction, Development, and Ex-Vivo Evaluation of Thermoresponsive Mucoadhesive In-Situ Nasal Gel Incorporating Lablab purpureus Mucilage and Pluronic F127 for Enhanced Intranasal Delivery of Diclofenac Sodium”

Background: Oral venlafaxine hydrochloride is widely used for depressive and anxiety disorders but is associated with dose-related adverse effects and peak–trough plasma fluctuations, and undergoes hepatic first-pass metabolism, which may contribute to tolerability limitations. Objective: To formulate venlafaxine HCl transdermal matrix patches using HPMC K15 and to evaluate the effect of polymer ratio and triethyl citrate concentration on physicomechanical properties, compatibility, dermal safety, and in-vitro release behavior. Methods: Six matrix patch formulations were prepared by solvent casting using an ethanol: dichloromethane (1:1) system with three drug-to-polymer ratios (0.5:0.7, 0.5:0.85, 0.5:1.0) and two plasticizer levels (triethyl citrate 0.05 or 0.15 mL). Patches were evaluated for weight variation, thickness, drug content, folding endurance, moisture loss/absorption, tensile strength, and related quality parameters. Drug–polymer compatibility was assessed by FTIR. Dermal irritation was tested in rabbits using Draize scoring. In-vitro release was assessed using USP apparatus II in phosphate buffer pH 7.4 at 32°C, with kinetic modeling using zero-order, first-order, Higuchi, and Korsmeyer–Peppas models. Results: Increasing HPMC ratio was associated with increased physicomechanical parameter values and slower in-vitro drug release, whereas higher triethyl citrate content was associated with improved flexibility and faster release. FTIR indicated no significant drug–polymer incompatibility, and rabbit testing showed no significant irritation. Conclusion: HPMC ratio and triethyl citrate concentration are key formulation determinants governing matrix patch quality and in-vitro release of venlafaxine HCl; further work should include quantitative statistical comparison and membrane-based permeation flux testing

The effect of magnesium aluminium silicate (MAS) on rheological, release and permeation characteristics of diclofenac sodium (DS) aqueous gels was investigated. DS aqueous gels were prepared using various gelling agents, such as 15% w/w poloxamer 407 (PM407), 1% w/w hydroxypropylmethylcellulose (HPMC), and 1% w/w high and low viscosity grades of sodium alginate (HV-SA and LV-SA, respectively). Different amounts of MAS (0.5, 1.0 and 1.5% w/w) were incorporated into the DS gels. Incorporation of MAS into the DS gels prepared using SA or PM407 caused a statistical increase in viscosity (P<0.05) and a shift from Newtonian flow to pseudoplastic flow with thixotropic property. The DS release rates of these composite gels were significantly decreased (P<0.05) when compared with the control gels. This was due to an interaction between MAS and PM407 or SA, and adsorption of DS onto MAS particles. Moreover, a longer lag time and no change in DS permeation flux were found when MAS was added to the gels. The findings suggest that the rheological characteristics of gels prepared using PM407 or SA could be improved by incorporating MAS. However, the use of MAS could retard the DS release and extend the lag time of DS permeation.

Objectives: The purpose of present research work was to develop mucoadhesive microparticles of Zaleplon for nasal delivery with the aim to avoid hepatic first-pass metabolism, improve therapeutic efficacy and enhance residence time in the treatment of insomnia. Materials and Methods: Chitosan-based microparticles were prepared by the coacervation method by varying the drug:polymer ratio. The microparticles were evaluated for particle size and shape and surface morphology by scanning electron microscopy, drug content, drug entrapment efficiency, swelling study, in vitro mucoadhesion, differential scanning calorimetric (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR), in vitro drug release study, and ex vivo drug permeation. Results: Zaleplon microparticles showed irregular-shaped particles and particle size was found to be in the range of 4.97–10.6 μm, which is favorable for intranasal absorption. The prepared microparticles exhibited a good swelling index. The percentage drug content and entrapment efficiency was found to be in the range between 36.36% - 80% and 37.65% - 52.88%, respectively. In vitro mucoadhesion was performed by adhesion number using goat nasal mucosa and was observed in a range from 43.33 ± 4.409 to 75 ± 2.886%. It was observed that polymer concentration enhancement led to increased mucoadhesive strength. The results of DSC and XRD studies revealed the molecular amorphous dispersion of Zaleplon into the chitosan microparticles. IR spectra of Zaleplon along with excipient showed no interaction between Zaleplon and excipients. In vitro drug release from all the formulations was biphasic, being characterized by a slight “burst” followed by slow release. At the end of 12 h, F6 (1:6) showed drug release of 81.66 ± 1.545%, indicating sustained release. The permeation data of formulation from goat nasal mucosa was found near to that obtained with dialysis membrane in vitro. Conclusion: According to the obtained results, Zaleplon loaded chitosan microparticles prepared by coacervation method proved to be capable of sustained release and could be used through nasal route as an alternative to oral administration.

The purpose of the current investigation was to develop chondroitin sulfate/carbopol-co-poly(acrylic acid) (CS/CBP-co-PAA) hydrogels for controlled delivery of diclofenac sodium (DS). Different concentrations of polymers chondroitin sulfate (CS), carbopol 934 (CBP), and monomer acrylic acid (AA) were cross-linked by ethylene glycol dimethylacrylate (EGDMA) in the presence of ammonium peroxodisulfate (APS) (initiator). The fabricated hydrogels were characterized for further experiments. Characterizations such as Scanning electron microscopy (SEM), Thermogravimetric analysis (TGA), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), and Fourier transform infrared spectroscopy (FTIR) were conducted to understand the surface morphology, thermodynamic stability, crystallinity of the drug, ingredients, and developed hydrogels. The swelling and drug release studies were conducted at two different pH mediums (pH 1.2 and 7.4), and pH-dependent swelling and drug release was shown due to the presence of functional groups of both polymers and monomers; hence, greater swelling and drug release was observed at the higher pH (pH 7.4). The percent drug release of the developed system and commercially available product cataflam was compared and high controlled release of the drug from the developed system was observed at both low and high pH. The mechanism of drug release from the hydrogels followed Korsmeyer–Peppas model. Conclusively, the current research work demonstrated that the prepared hydrogel could be considered as a suitable candidate for controlled delivery of diclofenac sodium.

Aqueous solubility of diclofenac diethylamine (DDEA), a nonsteroidal anti-inflammatory drug currently formulated as a topical emulgel, was studied in the presence of pharmaceutical additives and compared with diclofenac sodium (DS). Electrolytes at low concentrations exhibited a salting-in effect on DDEA with peak solubility that was attributed to the association of DDEA into micelles, followed by a salting-out effect at higher concentrations, by which structure formation by DDEA molecules increased and precipitation occurred. For DS, which is not capable of forming micelles, the salting-out effect was dominant due to the common ion effect. Cosolvents displayed significant enhancement in solubility of both salts except glycerol, which showed a slight increase in solubility of DDEA and a decrease in solubility of DS due to transformation into the less soluble hydrate form. Ethanol and polyethylene glycol (PEG) 400 cosolvent systems at all concentrations showed positive deviations from the log-linear solubility equation. In the case of propylene glycol (PG) cosolvent systems, negative deviations were observed at low volume fractions of cosolvent, while positive deviations were observed at high volume fractions of cosolvent for DS and DDEA. The parent drug, being less ionizable and highly nonpolar, showed negative deviations up to 90% PG content. Thus, the positive deviations for DS and DDEA could be attributed to the more ionizable carboxylic group and its higher ability for hydrogen bonding at higher fractions of cosolvent. Polyvinylpyrrolidone (PVP) and PEG4000 or PEG6000 enhanced the solubility of DS and DDEA, with PVP exerting higher solubilizing efficiency and DS showing better solubility than DDEA. Solubilities of DS in Tween 80 (T80) and Pluronic F-127 (PF127) aqueous solutions were almost similar, while the solubility of DDEA in the presence of T80 was higher than the solubility in the presence of PF127. DS appeared to be located more in the polyoxyethylene mantle of the micelles, while DDEA was located more in the core of the micelles.

A comparative investigation of release kinetics of paclitaxel from natural protein and macromolecular nanocarriers in nanoscale drug delivery systems

The aim of the present work was to formulation and evaluation of pH Triggered in-situ Ophthalmic Gel of Besifloxacin Hydrochloride to overcome the drawbacks obtained by conventional eye drop. There are two independent variables were used i.e. Carbopol 934 and HPMC K100. Carbopol 934 were used as gelling agent and HPMC K100 were used as bioadhesive polymer. Besifloxacin Hydrochloride shows activity against a wide range of Gram-positive and negative ocular pathogens: examples are Corynebacterium pseudodiphtheriticum, Moraxella lacunata, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae and Streptococcus salivarius. The in situ gelling system involves sol-to-gel transition in the cul-de-sac upon instillation to avoid pre corneal elimination. The formulations were prepared by 32 factorial design. The prepared formulations were evaluated for clarity, pH, viscosity, Bioadhesive strength of gel, gel strength gel, Drug Content, In-vitro Drug Release Study, Antibacterial Activity, Isotonicity Evaluation, HET-CAM Test and stability studies. The drug content was in the range of 97-99.57 %. Formulation F5 selected as optimized on the basis of evaluation. It shows highest drug release upto 8hrs. It shows good antibiotic activity against Staphylococcus aureus. The optimized formulation was isotonic with blood cells. It passes sterility test. The optimized formulation passes the ocular irritancy test i.e. HET-CAM Test. The formulation kept for the stability study for 3 months. Short term stability study indicates that room temperature 400±20 was appropriate storage condition for formulations.&#x0D; Keywords: pH Triggered, bioadhesive polymer, Carbopol 934, HPMC K100, HET-CAM Test, Antibacterial Activity.

The aim of the present work was development and characterization of in-situ Ophthalmic Gel of Bepotastine Besilate to overcome the drawbacks obtained by conventional eye drop. There are two independent variables were used i.e. Carbopol 934 and HPMC K100. Carbopol 934 were used as gelling agent and HPMC K100 were used as bioadhesive polymer. The in situ gelling system involves sol-to-gel transition in the cul-de-sac upon instillation to avoid pre corneal elimination. The formulations were prepared by 32 factorial design. The prepared formulations were evaluated for Clarity, pH, Viscosity, Bioadhesive strength of gel, Gel strength , Drug Content, In-vitro Drug Release Study, Isotonicity Evaluation, HET-CAM Test and stability studies. The drug content was in the range of 97-99.57 %. Formulation F5 selected as optimized on the basis of evaluation. It shows highest drug release upto 8 hours. It shows good antihistaminic activity against Staphylococcus aureus. The optimized formulation was isotonic with blood cells. It passes sterility test. The optimized formulation passes the ocular irritancy test i.e. HET-CAM Test. The formulation kept for the stability study for 3 months. Short term stability study indicates that room temperature 400±20 was appropriate storage condition for formulations. Keywords: pH Triggered, bioadhesive polymer, Carbopol 934, HPMC K100, HET-CAM Test , Isotonicity Evaluation.

The present study was aimed at developing Gastro retentive bilayer drug delivery systems containing esomeprazole and clarithromycin for the treatment of H. pylori induced gastric ulcer to minimize the side effect, improve the prolongation of action, to reduce the frequency of drug administration. The tablet is characterized by immediate release layer of esomeprazole and Gastroretentive layer of clarithromycin. The formulation containing Gastroretentive layer was designed using HPMC K 15, HPMC K4 and PVP K30 as floating agents, sodium bicarbonate and citric acid as gas-generating agent. Crospovidone, sodium starch glycolate and croscarmellose sodium was used as superdisintegrant for the preparation of immediate release layer. The prepared Gastroretentive layer was evaluated for their precompression parameters, physical characteristics like hardness, friability, uniformity of weight, uniformity of drug content, swelling index, In-vitro floating studies and In-vitro drug release. The release of the esomeprazole from the immediate release layer was found to be 89.98 % in 15minutes. The release of clarithromycin for the sustained release floating layer was found to be 98.89±0.47% in 12 hours. The data obtained from In-vitro release were fitted into the various kinetic models (Zero Order, Higuchi, First Order and Korsmeyer–Peppas Model). Keywords: Esomeprazole, Clarithromycin, Bilayer floating tab, Crospovidone, Superdisintegrant

In this study, bio-responsive polymeric MoS2 nanocomposites were prepared for use as a drug carrier for cancer therapy. Herein, we report the synthesis and demonstrate the self-assembly of pluronic F127 (PF127) on a cystamine–glutathione–MoS2 (CYS–GSH–MoS2) system, which can be used for GSH-triggered drug release under biological reducing conditions. The reduction-sensitive disulfide bond containing CYS was incorporated between the amphiphilic copolymer PF127 and GSH–MoS2 to achieve feasible drug release. Percent drug loading capacity and encapsulation efficiency were 51.3% and 56%, respectively. In addition, when the MoS2–GSH–CYS–PF127 nanocomposite was incubated in a GSH environment, the morphology of the nanocomposite tended to change, ultimately leading to drug release. The drug-loaded PF127–CYS–GSH–MoS2 polymeric nanocomposites efficiently released 52% of their drug content after 72 h of incubation in a GSH reduction environment. The HeLa cells treated with DOX loaded MoS2–GSH–CYS–PF127 showed 38% toxicity at drug concentration of 40 μg, which indicated that the successfully released of drug from carrier and caused the cell death. Further, fluorescence microscopy images of HeLa cells revealed the potential behavior of the MoS2–GSH–CYS–PF12 nanocomposite during the 2- and 4 h incubation periods; the nanocomposite was only found in the cytoplasm of HeLa cells. Interestingly, after 6 h of incubation, the drug was slowly released from the nanocomposite and could enter the nucleus as confirmed by fluorescence imaging of HeLa cells. Altogether, our synthesized PF127-coated MoS2 nanocomposite could be effectively adopted in the near future as a GSH-sensitive drug carrier.

The aim of this study was to prepare mucoadhesive vaginal tablets of clotrimazole for treatment of vaginal candidiasis. A combination of mucoadhesive polymers like HPMC K100M, Sodium CMC, and Eudragit L100 were used in different ratios prepare solid dispersions to enhance its solubility. Tablets were prepared by the wet granulation method. Solid dispersions were evaluated for saturation solubility. All tablet batches were evaluated for weight variation, hardness, friability, drug content, swelling index, in vitro drug release study, ex vivo diffusion and mucoadhesive strength. FTIR spectra showed there was no interaction between the drug and the excipients. HPMC K100 M increased the solubility of clotrimazole in simulated vaginal fluid at pH 4.5. Eudragit L100 was shown to increase the swelling and mucoadhesive strength of the tablet, i.e., 3.03 and 3.29 g. The in vitro and ex vivo release of all 9 batches showed between 61 to 78% release in 8h. Ex vivo diffusion studies using sheep vaginal membrane showed 43 to 59% in 6h in simulated vaginal fluid. The release and flux were nearly comparable to marketed tablet i.e., Candid-V6. The drug release of all batches followed the Korsmeyer-Peppas kinetic model, and the mechanism was found to be non‐Fickian/anomalous. Keywords: Clotrimazole, solid dispersion, HPMC K100M, Eudragit L100, Sodium CMC.

The aim of this research was to investigate the release behavior of a combination of two poorly water-soluble active pharmaceutical ingredients (APIs) from poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles. Amlodipine besylate - AML, a calcium channel blocker, and valsartan - VAL, an angiotensin II receptor antagonist drug, were used as poorly water-soluble model drugs. PLGA nanoparticles loaded with AML-VAL (1:16 w/w) were obtained by nanoprecipitation using an amphiphilic block copolymer - Pluronic F127 as stabilizer. The drugs release from the PLGA nanoparticles was determined by a dialysis membrane method under sink conditions. Nanoparticles provided a slow release for both APIs and an attenuated burst effect compared to free drug. Five kinetics models such as Zero-order, First-order, Korsmeyer-Peppas, Higuchi and Hixson-Crowell were applied to predict drug release profiles. The Higuchi and Korsmeyer-Peppas models (R 2 &gt; 0.97) best described physicochemical release phenomenon for each PLGA formulations.

The present investigation was aimed to develop a thermo-reversible nasal in situ gel of atomoxetine hydrochloride (AH) with reduced nasal muco-ciliary clearance in order to improve residence time and targeting the brain through nasal mucosa for the treatment of attention-deficit hyperactivity disorder (ADHD). In situ gel formulations were prepared using different concentrations of the thermo-gelling poloxamer 407 and mucoadhesive polymers. Temperature-triggered ionic gelation is the mechanism involved. Taguchi L9 OA experimental design was employed for the optimization of the effect of independent variables (Poloxamer 407 and Carbopol 934P) on the response (gelation temperature). In situ gel formulation F4 having 20% poloxamer 407 and 0.3% carbopol 934P and formulation F6 having 20% poloxamer 407 and 0.2% HPMC K100 were optimized based on evaluation parameters. The gelation temperature of F4 and F6 was found to be 37°C ± 0.4 and 37°C ± 0.2, drug content 98.34 and 98.33% and drug release was 83.18, 82.4% in 4 hrs with a flux of 436.9 and 428.1 μg.cm2/hr, respectively. The release pattern of drug followed first-order kinetics with Higuchi release mechanism. The value of ‘n’ from Korsemeyer equation indicated the anomalous diffusional drug release. This study concluded that in situ gel enhanced the nasal residence time and thus may improve the bioavailability of the drug through nasal route by avoiding first pass metabolism&#x0D; Dhaka Univ. J. Pharm. Sci. 18(2): 183-193, 2019 (December)

The present study is an attempt to formulate a controlled-release matrix tablet formulation for alfuzosin hydrochloride by using low viscous hydroxy propyl methyl cellulose (HPMC K-100 and HPMC 15cps) and its comparison with marketed product. Different batches of tablets containing 10 mg of alfuzosin were prepared by direct compression technique and evaluated for their physical properties, drug content, and in vitro drug release. All the formulations had a good physical integrity, and the drug content between the batches did not vary by more than 1%. Drug release from the matrix tablets was carried out for 12 hr and showed that the release rate was not highly significant with different ratios of HPMC K-100 and HPMC15cps. Similar dissolution profiles were observed between formulation F3 and the marketed product throughout the study period. The calculated regression coefficients showed a higher r2 value with zero-order kinetics and Higuchi model in all the cases. Although both the models could be applicable, zero-order kinetics seems to be better. Hence, it can be concluded that the use of low viscous hydrophilic polymer of different grades (HPMC K-100 and HPMC 15cps) can control the alfuzosin release for a period of 12 hr and was comparable to the marketed product.

Polymeric mucoadhesive pellets of nifedipine were designed using computer software and they were prepared by extrusion-spheronization using HPMC K15M and κ-carrageenan with microcrystalline cellulose. A randomized rotatable two factor central composite design was applied for assessment of influence of two independent variables such as concentration of κ-carrageenan and HPMC K15M on dependent variables. Pellets were characterized by FTIR, DSC, SEM, flow properties, particle size, abrasion resistance, sphericity, drug content, percent production yield, in vitro drug release, ex vivo mucoadhesion, stability studies and similarity factor. The optimized formulation was selected based on criteria of sphericity nearest to 1.0 with maximum cumulative drug release percentage. Formulation NF6 exhibited sufficient porous spheres, free flowing and smooth surface mucoadhesion of 91.34 % and drug content 98.22 ± 0.37 %. Kinetic modeling revealed that the formulation followed the Higuchi model and showed the Quassi-Fickian drug release mechanism. The similarity factor, F2 value, was found to be 74 ± 6 and there was no significant change in drug content and ex vivo mucoadhesion after 90 days at 40 ± 2 °C, and 75 ± 5 % RH clearly indicated the optimized batch NF6 was stable. Thus, it can be concluded that use of κ-carrageenan, microcrystalline cellulose and HPMC K15M at the 20:35:10 w/w ratio could provide an effective carrier for enhancement of sphericity and sustained release of matrix pellets.