Thermo-activated in situ rectal gel preparation for Ibuprofen Using Eutectic Mixture.

This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2% (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30°C to 36°C, with consistent amount of drug soluble in the formulations (93% - 110%). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18% poloxamer 407, 12% poloxamer 188, and 1% sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20% P407 & 10% P188) and FS15 (18% P407 & 12% P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.

Discrepancies in Open Access Fees within Pharmacology, Toxicology, and Pharmaceutics Journals.

Modern science has been transformed by open access (OA) publishing levied a significant economic burden on the authors. This article analyzes the discrepancies among OA publication fees in pharmacology, toxicology, and pharmaceutics. The observations comprise 160 OA journals and their corresponding Q ranking, SJR, H index, impact factor, country, and cost of publication. The OA fees were found to depend on the quality matrices, which was unexpected. Differences in OA fees raise ethical questions as OA fees are meant to cover the publication charges by the publishers or generate more revenues by taking advantage of the authors' temptation to publish in high-impact journals. Despite our findings being based on limited sample size and belonging to a particular field (pharmacy), it will shed considerable light on the issue of discrepancies among APCs charged by OA journals.

Preparation and evaluation of ßcyclodextrin-based nanosponges loaded with Budesonide for pulmonary delivery.

Budesonide (BUD) is a glucocorticosteroid used to treat chronic obstructive pulmonary disease. Despite this, it is a hydrophobic compound with low bioavailability. To address these hurdles, non-toxic and biocompatible ßcyclodextrin-based nanosponges (ßCD-NS) were attempted. BUD was loaded on five different ßCD-NS at four different ratios. NS with 1,1'-carbonyldiimidazole (CDI) as a crosslinking agent, presented a higher encapsulation efficiency ( Ì´ 80%) of BUD at 1:3 BUD: ßCD-NS ratio (BUD-ßCD-NS). The optimized formulations were characterized by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), water absorption capacity (WAC), scanning electron microscopy (SEM), X-ray powder diffraction studies (XRD), particle size, zeta potential, encapsulation efficiency, in vitro and in vivo release studies, acute toxicity study, solid-state characterization, and aerosol performance. In vitro-in vivo correlation and cytotoxicity of the formulations on alveolar cells in vitro were further determined. In vitro and in vivo studies showed almost complete drug release and drug absorption from the lungs in the initial 2 h for pure BUD, which were sustained up to 12 h from BUD loaded into nanosponges (BUD-ßCD-NS). Acute toxicity studies and in vitro cytotoxicity studies on alveolar cells proved the safety of BUD-ßCD-NS. Several parameters, including particle size, median mass aerodynamic diameter, % fine particle fraction, and % emitted dose, were evaluated for aerosol performance, suggesting the capability of BUD-ßCD-NS to formulate as a dry powder inhaler (DPI) with a suitable diluent. To sum up, this research will offer new insights into the future advancement of ßCD-NS as drug delivery systems for providing controlled release of therapeutic agents against pulmonary disease.

Development and In vitro Evaluation of Aceclofenac Buccal Film.

AIM: This study aimed to formulate and characterize aceclofenac buccal film formulations made of different polymers and evaluate the effects of polymer type on buccal film properties. MATERIALS AND METHODS: Five polymer types, namely hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (SCMC), polyvinyl alcohol (PVA), Eudragit S100, and Eudragit SR100, were used to prepare aceclofenac buccal film formulation either separately or combined by solvent-casting method. These formulations were evaluated in terms of physical appearance, folding test, film weight and thickness, drug content, percentage of elongation, moisture uptake, water vapor permeability, and in vitro drug release. RESULTS: The addition of Eudragit polymer in most of the produced buccal films was unacceptable with low folding endurance. However, the dissolution profile of buccal films made from PVA and Eudragit SR100 provided a controlled drug release profile. CONCLUSION: Buccal films can be formulated using different polymers either individually or in combination to obtain the drug release profile required to achieve a desired treatment goal. Furthermore, the property of the buccal films depends on the type and concentration of the polymer used.

Development of Clindamycin Loaded Oral Microsponges (Clindasponges) for Antimicrobial Enhancement: In Vitro Characterization and Simulated in Vivo Studies.

Clindamycin phosphate (CLP) is a broad-spectrum antibiotic that is used widely for different types of infections. It has a short half-life and hence it should be taken every six hours to ensure adequate antibiotic blood concentration. On the other hand, microsponges are extremely porous polymeric microspheres, offering the prolonged controlled release of the drug. The present study aims to develop and evaluate innovative CLP-loaded microsponges (named Clindasponges) to prolong and control the drug release and enhance its antimicrobial activity, consequently improving patient compliance. The clindasponges were fabricated successfully by quasi-emulsion solvent diffusion technique using Eudragit S100 (ES100) and ethyl cellulose (EC) as carriers at various drug-polymer ratios. Several variables were optimized for the preparation technique including the type of solvent, stirring time, and stirring speed. The clindasponges were then characterized in terms of particle size, production yield, encapsulation efficiency, scanning electron microscopy, Fourier Transform Infrared Spectroscopy analysis, in vitro drug release with kinetic modeling, and antimicrobial activity study. Moreover, in vivo, pharmacokinetics parameters of CLP from the candidate formula were simulated based on the convolution method and in vitro-in vivo correlation (IVIVC-Level A) was built up successfully. Uniform spherical microsponges with 82.3 µm mean particle size with a porous spongy structure were evident. ES2 batch exhibited the highest production yield and encapsulation efficiency (53.75 and 74.57%, respectively) and it was able to exhaust 94% of the drug at the end of 8 h of the dissolution test. The release profile data of ES2 was best fitted to Hopfenberg kinetic model. ES2 was significantly (p < 0.05) effective against Staphylococcus aureus and Escherichia coli compared to the control. Also, ES2 displayed a twofold increase in the simulated area under the curve (AUC) compared to the reference marketed product.

DDSolver Software Application for Quantitative Analysis of In vitro Drug Release Behavior of the Gastroretentive Floating Tablets Combined with Radiological Study in Rabbits.

BACKGROUND: Gastroretentive drug delivery systems (GRDDSs) are designed to release the drug in the stomach over a prolonged time; thus, they can reduce drug dosing frequency and dose size and improve patient compliance. GRDDSs are also highly effective in enhancing the bioavailability of the drug that exhibits window absorption in specific segments of the gastrointestinal (GI) tract. Famotidine (FMT), an H2 receptor antagonist, is an example of these drugs. FMT is a slightly watersoluble drug but well soluble in an acidic medium. This research aims to formulate FMT gastroretentive floating tablets (FMT-GRFTs) to improve the bioavailability and therapeutic activity of the drug and increase patients' adherence to treatment. In addition, the in vitro release behavior of the prepared FMT-GRFTs was quantitatively analyzed using the DDSolver software to assist in selecting the successful formulation that was then evaluated in vivo. METHODS: The direct compression technique prepared numerous tablet formulations and was subjected to the pre-and post-compression evaluation. Data of FMT dissolution in the simulated gastric medium was analyzed by various kinetic models built in the DDSolver program. In addition, the simulated pharmacokinetics (AUC, MDT, and MRT), R2 adjusted, AIC, MSC, correlation of the residuals, and similarity factor (f2) were also generated. RESULTS: The results revealed that FMT release from the candidate formula (FH3) fitted to the first-order kinetic model, with a high value of R2 adjusted and MSC and a low AIC. The release behavior exhibited the Fickian diffusion mechanism. The similarity factor showed no significant difference (p < 0.05) of the test sample compared to the reference product. Nevertheless, the simulated pharmacokinetic parameter, AUC, proved a two-fold enhancement in FMT bioavailability, with a significant increment in the MDT and MRT compared with the reference product.The FT-IR spectroscopy analysis indicated the absence of drug-excipients/polymer interaction.The in vivo X-ray studies on rabbits confirmed that the floating tablets showed nearly eight hours of gastric residence. CONCLUSION: DDSolver software was helpful in deciding the optimized formulation of FMT floating tablets. The radiological examination in rabbits for gastric retention was consistent with the release data analysis in vitro.

Stability of Paracetamol Instant Jelly for Reconstitution: Impact of Packaging, Temperature and Humidity.

The stability of the medicinal product is a major concern in the pharmaceutical industry and health authorities, whose goal is to guarantee that drugs are delivered to patients without loss of therapeutic properties. This study aims to evaluate the effect of environmental conditions and packaging on the stability of paracetamol instant jelly sachets based on both chemical and physical stability. The paracetamol instant jelly was packaged in plastic sachets (packaging 1) and sealed aluminium bags in screw-capped amber glass bottles (packaging 2), which were stored in real-time and accelerated stability chambers for 3 months. Samples were taken out from the chambers and were characterised for appearance, moisture content, texture, viscosity, in vitro drug release, paracetamol content, and 4-aminophenol level at different time points. The real-time storage condition at a lower temperature maintained the stability of the paracetamol instant jelly, while the accelerated condition led to a significant change in the formulation properties. In addition, the proper packaging of paracetamol instant jelly maintained the paracetamol's stability, regardless of environmental conditions, for three months. The results show that the environmental conditions and packaging play a significant role in maintaining paracetamol instant jelly stability.

Effect of Different Carriers on In Vitro and In Vivo Drug Release Behavior of Aceclofenac Proniosomes.

BACKGROUND: Improved bioavailability of Aceclofenac (ACE) may be achieved through proniosomes, which are considered as one of the most effective drug delivery systems and are expected to represent a valuable approach for the development of better oral dosage form as compared to the existing product. However, the carrier in this system plays a vital role in controlling the drug release and modulating drug dissolution. Accordingly, a comparative study on different carriers can give a clear idea about the selection of carriers to prepare ACE proniosomes. OBJECTIVE: This study aims to evaluate the role of maltodextrin, glucose, and mannitol as carriers for in vitro and in vivo performance of Aceclofenac (ACE) proniosomes. METHODS: Three formulations of proniosomes were prepared by the slurry method using the 100 mg ACE, 500 mg span 60, 250 mg cholesterol with 1300mg of different carriers, i.e., glucose (FN1), maltodextrin (FN2), and mannitol (FN3). In vitro drug release studies were conducted by the USP paddle method, while in vivo studies were performed in albino rats. Pure ACE was used as a reference in all the tests. Lastly, the results were analyzed using the High-Pressure Liquid Chromatography (HPLC) method, and data were evaluated using further kinetic and statistical tools. RESULTS: No significant differences (p > 0.05) in entrapment efficiency (%EE) of FN1, FN2, and FN3 (82 ± 0.5%, 84 ± 0.66%, and 84 ± 0.34% respectively) were observed and formulations were used for further in vitro and in vivo evaluations. During in vitro drug release studies, the dissolved drug was found to be 42% for the pure drug, while 70%, 17%, and 30% for FN1, FN2, and FN3, respectively, at 15 min. After 24 hrs, the pure drug showed a maximum of 50% release while 94%, 80%, and 79% drug release were observed after 24 hr for FN1, FN2, and FN3, respectively. The in vivo study conducted on albino rats showed a higher Cmax and AUC of FN1 and FN2 in comparison with the pure ACE. Moreover, the relative oral bioavailability of proniosomes with maltodextrin and glucose as carriers compared to the pure drug was 183% and 112%, respectively. Mannitol- based formulation exhibited low bioavailability (53.7%) that may be attributed to its osmotic behavior. CONCLUSION: These findings confirm that a carrier plays a significant role in determining in vitro and in vivo performance of proniosomes and careful selection of carrier is an important aspect of proniosomes optimization.

Optimization of Aceclofenac Proniosomes by Using Different Carriers, Part 1: Development and Characterization.

In the contemporary medical model world, the proniosomal system has been serving as a new drug delivery system that is considered to significantly enhance the bioavailability of drugs with low water solubility. The application of this system can improve the bioavailability of aceclofenac that is used for the relief of pain and inflammation in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. The present study is intended to develop an optimized proniosomal aceclofenac formula by the use of different carriers. Aceclofenac proniosomes have been prepared by slurry method, and different carriers such as maltodextrin, mannitol, and glucose were tried. Prepared proniosomes characterized by differential scanning calorimetry (DSC) analysis and Fourier transform infrared (FTIR) analysis revealed the compatibility of the drug chosen with the ingredient added, powder X-ray diffractometry (XRD) confirmed the amorphous phase of the prepared proniosomes, and finally, the surfactant layer was observed by scanning electron microscopy (SEM). Aceclofenac physical state transformations were confirmed with all formulas but maltodextrin proniosomes exhibited solubility more than other formulations. HPLC method has been used to analyze the niosomes derived from proniosomes in terms of their entrapment capability and drug content. The obtained results revealed that aceclofenac proniosomes can be successfully prepared by using different carriers.