Formulation and evaluation of miconazole lipogel for enhanced drug permeation.

Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance drug permeability using dimethyl Sulfoxide (DMSO). The miconazole lipogels, A1 (without DMSO) and A2 (with DMSO) were formulated and evaluated for organoleptic evaluation, pH, viscosity, stability studies, freeze-thawing, drug release profile and drug permeation enhancement. Results had stated that prepared lipogel's pH falls within the acceptable range required for topical delivery (4 to 6) while both formulations show good results in organoleptic evaluation. The A2 formulation containing DMSO shows better permeation of miconazole (84.76%) on the artificial skin membrane as compared to A1 lipogel formulation (50.64%). In in-vitro drug release studies, A2 for-mulation showed 87.48% drug release while A1 showed just 60.1% drug release from lipogel. Stability studies were performed on model formulations under environmental conditions and both showed good spreadibility, stable pH, free of grittiness and good consistency in formulation. The results concluded that A2 formulation containing DMSO shows better results as compared to DMSO-free drug lipogel.

A comprehensive review on transethosomes as a novel vesicular approach for drug delivery through transdermal route.

Drug delivery through transdermal route is one of the effective methods for the application of drugs. It overcomes many drawbacks which are encountered with the oral route. Moreover, many drugs are not able to pass through the stratum corneum, which is the main barrier for the transdermal drug delivery. Formation of ultra-deformable vesicles (UDVs) is a novel technique for the transdermal applications of the drugs. Transethosomes (TEs), ethosomes, and transferosomes are all part of the UDV. Because of the presence of increased concentrations of ethanol, phospholipids, and edge activators, TEs provide improved drug permeation through the stratum corneum. Because of the elasticity of TEs, drug penetration into the deeper layer of skin also increases. TEs can be prepared using a variety of techniques, including the cold method, hot method, thin film hydration method, and the ethanol injection method. It increases patient adherence and compliance because it is a non-invasive procedure of administering drugs. Characterization of the TEs includes pH determination, size and shape, zeta potential, particle size determination, transition temperature, drug content, vesicle stability, and skin permeation studies. These vesicular systems can be utilized to deliver a variety of medications transdermally, including analgesics, antibiotics, antivirals, and anticancer and arthritis medications. This review aims to describe vesicular approaches that had been used to overcome the barrier for the transdermal delivery of drug and also describes brief composition, method of preparation, characterization tests, mechanism of penetration of TEs, as well as highlighted various applications of TEs in medicine.

Formulation of Aloe vera based curcumin topical gel and its in-vitro evaluation.

Curcumin is a polyphenolic compound obtained from the rhizome of plant. Curcuma longa possesses antioxidant, anti-inflammatory and wound-healing properties. The current study was designed to formulate an Aloe vera-based curcumin topical gel. To enhance curcumin's solubility, it was first complexed with ß-cyclodextrin, given its hydrophobic nature. While Carbopol, carboxy methyl cellulose and guar gum were used in various concentrations as gelling agents for preparation of the formulations. The effect of propylene glycol as a permeation enhancer was also observed. The prepared formulations were tested for different parameters such as physical appearance, spreadability, drug content, pH, viscosity and in-vitro permeation. All the formulations were found to be stable. All formulations consisting of propylene glycol showed permeation within the range of 80-90%. The maximum percentage of drug release was observed in the formulation containing 1% Carbopol 940 as the gelling agent which also exhibited good spreadability. In comparison to gels formulated with carboxymethyl cellulose and guar gum, Carbopol 940 gels appeared more translucent. Consequently, it was concluded that curcumin's permeation improved following its complexation with ß-cyclodextrin. This complex when further used for the formation of an aloe vera based topical gel with 1% Carbopol 940 and 10% propylene glycol demonstrated maximum efficacy.

Thermo-Responsive Sol-Gel-Based Nano-Carriers Containing Terbinafine HCl: Formulation, In Vitro and Ex Vivo Characterization, and Antifungal Activity.

The current research aims to create a sol-gel-based nanocarrier containing terbinafine formulated for transdermal delivery of the drug into the skin. Sol-gel-based nanocarriers were prepared via the cold method using poloxamer-188, poloxamer-407, and distilled water. The prepared formulation was examined for pH, gelation temperature, Fourier transform infrared spectrophotometer (FTIR) analysis, thermal stability analysis, X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size analysis, zeta potential, and anti-microbial activity. The in-vitro drug release study of F1 was found to be 94%, which showed greater drug release as compared to F2 and F3. The pH of the formulation was found to be within the range applicable to the skin. The gelation temperature was detected at 28 °C. The SEM images of formulations have spotted various particles well-segregated from each other. Analysis of formulations showed a mean globule size diameter of 428 nm, zeta potential values of 0.04 mV, refractive index (1.329), and viscosity (5.94 cP). FTIR analysis confirmed various functional groups' presence in the prepared formulation. Thermal analysis has confirmed the stability of the drug within the prepared formulation. The growth of inhibition was found to be 79.2% in 60 min, which revealed that the prepared formulation has shown good permeation from the membrane. Hence, the sol-gel-based nanocarrier formulation of terbinafine was successfully developed and evaluated.

Tetrapodal ZnO-Based Composite Stents for Minimally Invasive Glaucoma Surgery.

The glaucoma burden increases continuously and is estimated to affect more than 100 million people by 2040. As there is currently no cure to restore the optic nerve damage caused by glaucoma, the only controllable parameter is the intraocular pressure (IOP). In recent years, minimally invasive glaucoma surgery (MIGS) has emerged as an alternative to traditional treatments. It uses micro-sized drainage stents that are inserted through a small incision, minimizing the trauma to the tissue and reducing surgical and postoperative recovery time. However, a major challenge for MIGS devices is foreign body reaction and fibrosis, which can lead to a complete failure of the device. In this work, the antifibrotic potential of tetrapodal ZnO (t-ZnO) microparticles used as an additive is elucidated by using rat embryonic fibroblasts as a model. A simple, direct solvent-free process for the fabrication of stents with an outer diameter of 200-400 µm is presented, in which a high amount of t-ZnO particles (45-75 wt %) is mixed into polydimethylsiloxane (PDMS) and a highly viscous polymer/particle mixture is extruded. The fabricated stents possess increased elastic modulus compared to pure PDMS while remaining flexible to adapt to the curvature of an eye. In vitro experiments showed that the fibroblast cell viability was inhibited to 43 ± 3% when stents with 75 wt % t-ZnO were used. The results indicate that cell inhibiting properties can be attributed to an increased amount of protruding t-ZnO particles on the stent surface, leading to an increase in local contacts with cells and a disruption of the cell membrane. As a secondary mechanism, the released Zn ions could also contribute to the cell-inhibiting properties in the close vicinity of the stent surface. Overall, the fabrication method and the antifibrotic and mechanical properties of developed stents make them promising for application in MIGS.

Development of Statistically Optimized Chemically Cross-Linked Hydrogel for the Sustained-Release Delivery of Favipiravir.

Nowadays, the use of statistical approaches, i.e., Box-Bhenken designs, are becoming very effective for developing and optimizing pharmaceutical drug formulations. In the current work, a Box-Bhenken design was employed using Design Expert version 11 to develop, evaluate, and optimize a hydrogel-based formulation for sustained release of an antiviral drug, i.e., favipiravir. The hydrogels were prepared using the free radical polymerization technique. ß-Cyclodextrin (ß-CD), N,N'-methylenebisacrylamide (MBA), acrylic acid (AA), and potassium per sulfate (KPS) were used as oligomer, crosslinker, monomer, and initiator, respectively. Three variables, including ß-CD (X1), MBA (X2), and AA (X3) were used at various concentrations for the preparation of hydrogels, followed by evaluation of a sol-gel fraction, swelling, porosity, chemical compatibilities, in vitro drug release, and entrapment efficiency. The results of the studies revealed that the degree of swelling was pH dependent, the best swelling being at pH 7.2 (1976%). On the other hand, for the low sol fraction of 0.2%, the reasonable porosity made the hydrogel capable of loading 99% favipiravir, despite its hydrophobic nature. The maximum entrapment efficiency (99%) was observed in optimized hydrogel formulation (F15). Similarly, in vitro drug release studies showed that the prepared hydrogels exhibited a good, sustained release effect till the 24th hour. The kinetic modelling of drug release data revealed that the Korsmeyer-Peppas model was best fit model, describing a diffusion type of drug release from the prepared hydrogels. Conclusively, the outcomes predict that the hydrogel-based system could be a good choice for developing a sustained-release, once-daily dosage form of favipiravir for improved patient compliance.

Clinical Response of Nuberol Forte® for Pain Management With Musculoskeletal Conditions in Routine Pakistani Practice (NFORTE-EFFECT).

Background Musculoskeletal pain is the most common complaint presented to the health practitioner. It is well-known that untreated or under-treated pain can have a significant negative impact on an individual's quality of life (QoL). Objectives The current study aimed to assess the clinical response of Nuberol Forte® (paracetamol 650 mg + orphenadrine 50 mg) to musculoskeletal pain in routine Pakistani practice and its impact on improving the patient's QoL. Methods A prospective, observational multicenter study (NFORT-EFFECT: Safety & Efficacy of Nuberol Forte in Pain Management). Three hundred ninety-nine patients with known prescreened musculoskeletal pain were recruited from 10 major healthcare facilities across six (6) major cities of Pakistan, as per the inclusion/exclusion criteria. After the baseline visit (Visit 1), the patients were followed up one to two weeks (Visit 2) after the treatment as per the physician's discretion. Data were collected using the Case Report Form (CRF) designed for the study, and adverse events (AEs) were also monitored to assess drug safety. Pain intensity was assessed through a visual analog scale (VAS), and QoL was assessed using the Muscle and Joint Measure (MJM) scale. Results Out of 399 enrolled patients, 49.4% were males and 50.6% were females with a mean age of 47.24 ± 14.20 years. Most patients were presented with knee osteoarthritis (OA), i.e., 148 (38%), followed by backache 70 (18.2%). A significant reduction in the mean pain score was observed after treatment with the combination of paracetamol and orphenadrine (p<0.05). Furthermore, an overall improvement in the patient's QoL was also observed. During the study, only 10 patients reported mild adverse events (AEs), namely, dryness of the mouth, dizziness, gastric irritation, tachycardia, restlessness, etc. Conclusion The combination of paracetamol and orphenadrine (Nuberol Forte) exhibited effective pain management among patients with musculoskeletal conditions and improved their QoL.

Anti myelosuppressant and hematopoietic activities of ethanolic fraction obtained from seeds of Carica papaya L.

Bone marrow suppression is one of the serious consequences of treatment with cytotoxic chemotherapeutic agents such as doxorubicin (DOX). It is very difficult to treat bone marrow suppression caused by anti-cancer drugs. This study was aimed to evaluate hematological effects particularly the antimyelosuppressant effects of ethanolic extract of papaya seeds at 200, 400 and 600 mg/kg daily dose for three weeks in doxorubicin induced hematopoietic suppression in rat model. Hematological parameters were assessed on weekly basis on days 0, 1, 7, 14 and 21. The alcoholic extract was found to cause remission of induced myelosuppression as indicated by a dose dependent increase in WBCs, neutrophils, lymphocytes, platelets, RBCs, Hb, hematocrit & mean corpuscular volume. However, the maximum dose (600mg/kg) of the extract showed maximum activity (p<0.05) in normalizing hematological parameters when compared with group B (induced group) and group A (controlled animals). These effects were compareable with those produced by Filgrastim 5µgm/kg used as standard or reference drug during these experiments. It is concluded from the results that papaya seeds possess myelostimulant activity and can be used to treat myelosuppression caused by chemotherapy. The drug can also be used for curing anemia, thrombocytopenia and immunological disorders characterized by myelosuppression.