Designing an ideal alcohol-based hand sanitizer: in vitro antibacterial responses of ethanol and isopropyl alcohol solutions to changing composition

This study aimed to achieve an in vitro quantification of the effects of composition and formulation factors on the killing rates of alcohol-based hand sanitizers. The killing rates of 85% ethyl alcohol (ET) and isopropyl alcohol (IPA) were studied under different conditions such as pH, electrolyte concentration, or inclusion of herbal extracts (cucumber, carrot, and aloe vera), a quaternary ammonium compound, or thickener over different time intervals. Changes in the activities were retested after 3 months as an indication of stability. From two-way ANOVA, both the time of exposure and the sanitizer type affected the activity against Staphylococcus aureus (P = 0.001 for both alcohols), whereas for Escherichia coli, time of exposure was significant (P = 0.027), while sanitizer type was less significant (P = 0.063). Extreme pHs, the presence of ions, and the inclusion of additives such as benzalkonium chloride (BAC), plant extracts, or carbomer impacted the 3-month activity of the samples differently. Important differences existing in the activities of ET and IPA, as a function of formulation factors or use conditions have been quantified using in vitro methods. Formulations should best be tailored for particular purposes and the all-purpose hand sanitizer may not exist. Graphic Abstract

Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model

Selective laser sintering (SLS) is a rapid prototyping technique for the production of three-dimensional objects through selectively sintering powder-based layer materials. The aim of the study was to investigate the effect of energy density (ED) and formulation factors on the printability and characteristics of SLS irbesartan tablets. The correlation between formulation factors, ED, and printability was obtained using a decision tree model with an accuracy of 80%. FT-IR results revealed that there was no interaction between irbesartan and the applied excipients. DSC results indicated that irbesartan was present in an amorphous form in printed tablets. ED had a significant influence on tablets’ physical, mechanical, and morphological characteristics. Adding lactose monohydrate enabled faster drug release while reducing the possibility for printing with different laser speeds. However, formulations with crospovidone were printable with a wider range of laser speeds. The adjustment of formulation and process parameters enabled the production of SLS tablets with hydroxypropyl methylcellulose with complete release in less than 30 min. The results suggest that a decision tree could be a useful tool for predicting the printability of pharmaceutical formulations. Tailoring the characteristics of SLS irbesartan tablets by ED is possible; however, it needs to be governed by the composition of the whole formulation.

A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy

An increasing number of studies published so far have evidenced the benefits of Simvastatin (SIM) and Doxorubicin (DOX) co-treatment in colorectal cancer. In view of this, the current study aimed to investigate the pharmaceutical development of liposomes co-encapsulating SIM and DOX, by implementing the Quality by Design (QbD) concept, as a means to enhance the antiproliferative effect of the co-formulation on C26 murine colon cancer cells co-cultured with macrophages. It is known that the quality profile of liposomes is dependent on the critical quality attributes (CQAs) of liposomes (drug entrapped concentration, encapsulation efficiency, size, zeta potential, and drug release profile), which are, in turn, directly influenced by various formulation factors and processing parameters. By using the design of experiments, it was possible to outline the increased variability of CQAs in relation to formulation factors and identify by means of statistical analysis the material attributes that are critical (phospholipids, DOX and SIM concentration) for the quality of the co-formulation. The in vitro studies performed on a murine colon cancer cell line highlighted the importance of delivering the optimal drug ratio at the target site, since the balance antiproliferative vs. pro-proliferative effects can easily be shifted when the molar ratio between DOX and SIM changes.

RESVERATROL-HUMIC ACID LOADED COLLOIDAL POLYMERIC NANOPARTICLES: DESIGN OF EXPERIMENT AND IN VITRO EVALUATION

Objective: The study aims at fabrication and optimization of co-encapsulated resveratrol and humic acid in colloidal polymeric nanocarriers to improves the stability of insoluble antioxidant, resveratrol. Methods: The Eudragit E100 polymeric material was used to fabricate oral co-encapsulation of resveratrol and humic acid in colloidal polymeric nanocarriers, called Res-HA-co-CPNs by an emulsification-diffusion-evaporation method. Taguchi orthogonal array design was employed to check the effect of formulation factors on in vitro physicochemical characteristics. The optimized formulation was further evaluated for stability studies at different conditions. Results: Optimized Res-HA-co-CPNs demonstrated spherical and smooth surface including mean PS 120.56±18.8 nm, PDI 0.122, ZP+38.25mV, and EE 82.37±1.49%. Solid-state characterizations confirmed that optimized Res-HA-co-CPNs showed amorphous characteristics. In vitro release profile of Res-HA-co-CPNs showed an outstanding sustained release behavior up to 48h and remain stable at the refrigerated condition for 6 mo. Conclusion: Res-HA-co-CPNs would be a proficient and promising dosage form for increasing the stability of insoluble antioxidants, resveratrol.

Formulation and Evaluation of Captopril Mouth Dissolving Film

The goal of this research is to develop captopril mouth dissolving films and evaluate the impact of various formulation factors on the physical and mechanical properties of the films, as well as drug release behaviour. In different grades, hydroxypropyl methyl cellulose (HPMC E15 and K4M) was employed as the film forming polymer. Formulation disintegration times were determined to be in the range of (52 2.5 to 125.6 2.02 s). Formula F2 had the fastest disintegration time in vitro (52 2.5 s) and was determined to be acceptable for film production with ideal physicochemical qualities, faster disintegration, and optimal in vitro release. It may be concluded that the solvent casting approach can be used to make captopril mouth dissolving films with a higher dissolution rate and greater patient compliance.

A study on the influence of the formulation factors on in vitro release of ketoprofen from sustained release tablets

Objectives. The aim of this study was to investigate the influence of formulation factors on in vitro release of ketoprofen from sustained release inert matrix tablets. Materials and methods. Laboratory scale, Ketoprofen sustained release inert matrix tablets were manufactured using Kollidon® SR as matrix formator, by direct tableting of powder blends. The influence of the formulation factors (X1 – matrix formator excipient and X2 – diluent type) on in vitro release of ketoprofen from sustained release tablets was studied by using a full factorial 23 experimental plan. Outcomes. Pharmacotechnical characterization of manufactured laboratory scale batches was performed and all 12 batches fulfilled European Pharmacopeia requests. In vitro release showed a sustained release profile in all cases. Variance analysis (ANOVA) showed a good correlation between experimental conditions and answers. In vitro release testing was performed in phosphate buffer pH = 7.4. Percentage release was determined spectrophotometrically at 258 nm. A decrease in the rate of in vitro release was registered, up to 4 h and 6 h when lactose DC and mannitol DC were used as diluents, respectively. Isomalt DC has increased the rate of in vitro release up to 6 h. Conclusions. In vitro release data, corresponding to formulation N1 shoed a good fitting with Weitbull, Korshmeyer-Peppas and Higuchi models while in vitro release data corresponding to formulation N8 presented a good fitting with Weitbull and Korsmeyer-Peppas. In case of formulations N1 and N8 a non-Fickian diff usion mechanism seems to be involved in drug release from the matrix tablets.

Alcohol-Based Hand Sanitizers in COVID-19 Prevention: A Multidimensional Perspective

The global use of alcohol-based hand sanitizers (ABHS) as an important means of controlling the transmission of infectious disease has increased significantly as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. This paper discusses the interplay between ABHS input (formulation) factors and output (product performance) factors in the context of a multidimensional perspective using a novel representative paradigm. In the model, represented in the form of a three-dimensional tetrahedron, each of the faces represents inputs in the manufacturing of the ABHS product, which are the type and amount of alcohol, the inactive ingredients, the formulation and the manufacturing practices. The four corners of the tetrahedron represent the product performance factors which include product efficacy, sensory characteristics, usage and compliance and product safety. The multidimensional approach to the formulation and evaluation of ABHS shows that several factors contribute to the effectiveness and utility of these products. The paradigm provides a useful framework for manufacturers of ABHS and related healthcare products.

UNDERSTANDING EFFECT OF LASER SPEED AND FORMULATION FACTORS ON PRINTABILITY AND CHARACTERISTICS OF SLS IRBESARTAN TABLETS- APPLICATION OF DECISION TREE MODEL 2021ICCBIKG (2021)

Selective laser sintering (SLS) is a rapid prototyping technique for the production of 3D objects through selectively sintering powder-based layers materials by combinations of energy from the laser beam and the heated chamber of the printer. The aim of the study was to investigate the effect of laser speed and formulation factors on printability and characteristics of SLS irbesartan tablets. Physical mixtures of hydroxypropylmethylcellulose (46-91%), Candurin® Gold Sheen (3%), colloidal silicon dioxide (1%), and irbesartan (5%) were prepared. Afterward, crospovidone (1-5%), Kollidon®VA 64 Fine (20%), and/or lactose monohydrate (20-45%) were added. Sintratec Kit SLS printer (Sintratec AG, Switzerland) was used for printing tablets. The decision tree model was applied to classify printability factors. Characterization of tablets was done in terms of physicochemical, mechanical and biopharmaceutical characteristics. Correlation between formulation factors, laser speed, and printability was obtained using decision tree model with an accuracy of 80%. FTIR results revealed that there was no interaction between irbesartan and applied excipients. DSC indicated that irbesartan was present in an amorphous form in printed tablets. It was observed that laser speed had a negative effect on weight. Tuning the drug release by laser speed was possible although lactose monohydrate reduced its impact because it was required higher energy for the sintering process. Results suggest that decision tree could be useful tool for predicting the printability of pharmaceutical formulations. Tailoring characteristics of SLS irbesartan tablets by laser speed is possible, however, it needs to be governed by the composition of the whole formulation.