Development and comparison of machine learning models for in-vitro drug permeation prediction from microneedle patch.

The field of machine learning (ML) is advancing to a larger extent and finding its applications across numerous fields. ML has the potential to optimize the development process of microneedle patch by predicting the drug release pattern prior to its fabrication and production. The early predictions could not only assist the in-vitro and in-vivo experimentation of drug release but also conserve materials, reduce cost, and save time. In this work, we have used a dataset gleaned from the literature to train and evaluate different ML models, such as stacking regressor, artificial neural network (ANN) model, and voting regressor model. In this study, models were developed to improve prediction accuracy of the in-vitro drug release amount from the hydrogel-type microneedle patch and the in-vitro drug permeation amount through the micropores created by solid microneedles on the skin. We compared the performance of these models using various metrics, including R-squared score (R2 score), root mean squared error (RMSE), and mean absolute error (MAE). Voting regressor model performed better with drug permeation percentage as an outcome feature having RMSE value of 3.24. In comparison, stacking regressor have a RMSE value of 16.54, and ANN model has shown a RMSE value of 14. The value of permeation amount calculated from the predicted percentage is found to be more accurate with RMSE of 654.94 than direct amount prediction, having a RMSE of 669.69. All our models have performed far better than the previously developed model before this research, which had a RMSE of 4447.23. We then optimized voting regressor model's hyperparameter and cross validated its performance. Furthermore, it was deployed in a webapp using Flask framework, showing a way to develop an application to allow other users to easily predict drug permeation amount from the microneedle patch at a particular time period. This project demonstrates the potential of ML to facilitate the development of microneedle patch and other drug delivery systems.

Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems.

Active pharmaceutical ingredients (API) with unfavorable physicochemical properties and stability present a significant challenge during their processing into final dosage forms. Cocrystallization of such APIs with suitable coformers is an efficient approach to mitigate the solubility and stability concerns. A considerable number of cocrystal-based products are currently being marketed and show an upward trend. However, to improve the API properties by cocrystallization, coformer selection plays a paramount role. Selection of suitable coformers not only improves the drug's physicochemical properties but also improves the therapeutic effectiveness and reduces side effects. Numerous coformers have been used till date to prepare pharmaceutically acceptable cocrystals. The carboxylic acid-based coformers, such as fumaric acid, oxalic acid, succinic acid, and citric acid, are the most commonly used coformers in the currently marketed cocrystal-based products. Carboxylic acid-based coformers are capable of forming the hydrogen bond and contain smaller carbon chain with the APIs. This review summarizes the role of coformers in improving the physicochemical and pharmaceutical properties of APIs, and deeply explains the utility of afore-mentioned coformers in API cocrystal formation. The review concludes with a brief discussion on the patentability and regulatory issues related to pharmaceutical cocrystals.

Current Trends in API Co-Processing: Spherical Crystallization and Co-Precipitation Techniques.

Active Pharmaceutical Ingredients (APIs) do not always exhibit processable physical properties, which makes their processing in an industrial setup very demanding. These issues often lead to poor robustness and higher cost of the drug product. The issue can be mitigated by co-processing the APIs using suitable solvent media-based techniques to streamline pharmaceutical manufacturing operations. Some of the co-processing methods are the amalgamation of API purification and granulation steps. These techniques also exhibit adequate robustness for successful adoption by the pharmaceutical industry to manufacture high quality drug products. Spherical crystallization and co-precipitation are solvent media-based co-processing approaches that enhances the micromeritic and dissolution characteristics of problematic APIs. These methods not only improve API characteristics but also enable direct compression into tablets. These methods are economical and time-saving as they have the potential for effectively circumventing the granulation step, which can be a major source of variability in the product. This review highlights the recent advancements pertaining to these techniques to aid researchers in adopting the right co-processing method. Similarly, the possibility of scaling up the production of co-processed APIs by these techniques is discussed. The continuous manufacturability by co-processing is outlined with a short note on Process Analytical Technology (PAT) applicability in monitoring and improving the process.

Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs.

Stability is an essential quality attribute of any pharmaceutical formulation. Poor stability can change the color and physical appearance of a drug, directly impacting the patient's perception. Unstable drug products may also face loss of active pharmaceutical ingredients (APIs) and degradation, making the medicine ineffective and toxic. Moisture content is known to be the leading cause of the degradation of nearly 50% of medicinal products, leading to impurities in solid dose formulations. The polarity of the atoms in an API and the surface chemistry of API particles majorly influence the affinity towards water molecules. Moisture induces chemical reactions, including free water that has also been identified as an important factor in determining drug product stability. Among the various approaches, crystal engineering and specifically co-crystals, have a proven ability to increase the stability of moisture-sensitive APIs. Other approaches, such as changing the salt form, can lead to solubility issues, thus making the co-crystal approach more suited to enhancing hygroscopic stability. There are many reported studies where co-crystals have exhibited reduced hygroscopicity compared to pure API, thereby improving the product's stability. In this review, the authors focus on recent updates and trends in these studies related to improving the hygroscopic stability of compounds, discuss the reasons behind the enhanced stability, and briefly discuss the screening of co-formers for moisture-sensitive drugs.

Continuous Manufacturing and Molecular Modeling of Pharmaceutical Amorphous Solid Dispersions.

Amorphous solid dispersions enhance solubility and oral bioavailability of poorly water-soluble drugs. The escalating number of drugs with poor aqueous solubility, poor dissolution, and poor oral bioavailability is an unresolved problem that requires adequate interventions. This review article highlights recent solubility and bioavailability enhancement advances using amorphous solid dispersions (ASDs). The review also highlights the mechanism of enhanced dissolution and the challenges faced by ASD-based products, such as stability and scale-up. The role of process analytical technology (PAT) supporting continuous manufacturing is highlighted. Accurately predicting interactions between the drug and polymeric carrier requires long experimental screening methods, and this is a space where computational tools hold significant potential. Recent advancements in data science, computational tools, and easy access to high-end computation power are set to accelerate ASD-based research. Hence, particular emphasis has been given to molecular modeling techniques that can address some of the unsolved questions related to ASDs. With the advancement in PAT tools and artificial intelligence, there is an increasing interest in the continuous manufacturing of pharmaceuticals. ASDs are a suitable option for continuous manufacturing, as production of a drug product from an ASD by direct compression is a reality, where the addition of multiple excipients is easy to avoid. Significant attention is necessary for ongoing clinical studies based on ASDs, which is paving the way for the approval of many new ASDs and their introduction into the market.

Enzyme-assisted metal nanoparticles etching based plasmonic ELISA: Progress and insights.

The unique size and shape tunable localized surface plasmon resonance (LSPR) properties of the noble metal nanoparticle have been extensively exploited to realize a variety of enzyme-based optical biosensors. Although approaches like metal film deposition, nanoparticle aggregation, and synthesis & growth of metal nanoparticles are quite useful, metal nanoparticle etching-based biosensors offer greater sensitivity, selectivity, and stability against various environmental factors which makes this strategy easy to use for field applications. This review discusses the current state-of-art of plasmonic nanoparticle etching-based enzyme-linked immunosorbent assay (ELISA) realized for visual detection of various analytes. The naked eye detection, i.e. without any optical readout device, is the additional advantage of this sensing approach that reduces the analysis cost significantly making it feasible under resource-constrained settings. This review paper provides deeper insights into biocatalytic etching mechanisms of various plasmonic nanoparticles resulting in vivid color change as a function of analyte concentration. Although nanoparticle etching-based ELISA has huge potential, steps need to be taken to realize a point-of-care (POC) nanodiagnostic before its translation to a commercial technique or product that can be achieved in near future by integrating it with microfluidics technology and other technological avenues.

Fast Absorbing Gut Suture versus Cyanoacrylate Tissue Adhesive in the Epidermal Closure of Linear Repairs Following Mohs Micrographic Surgery.

BACKGROUND: Cyanoacrylate topical adhesives and fast absorbing gut sutures are increasingly utilized by dermatologic surgeons as they provide satisfactory surgical outcomes while eliminating an additional patient visit for suture removal. To date, no head-to-head studies have compared the wound healing characteristics of these epidermal closure techniques in the repair of facial wounds after Mohs micrographic surgery. OBJECTIVE: To compare the cosmetic outcome of epidermal closure by cyanoacrylate topical adhesive with fast absorbing gut suture in linear repairs of the face following Mohs micrographic surgery. METHODS: Fourteen patients with wound length greater than 3cm who underwent Mohs micrographic surgery for nonmelanoma skin cancer of the face were enrolled in this randomized right-left comparative study. Following placement of dermal sutures, half of the wound was randomly selected for closure with cyanoacrylate and the contralateral side with fast absorbing gut suture. Using photographs from the three-month postoperative visit, six blinded individuals rated the overall cosmetic outcome. RESULTS: The present study shows no significant difference in cosmetic outcomes between cyanoacrylate and fast absorbing gut suture for closure of linear facial wounds resulting from Mohs micrographic surgery. Cyanoacrylate tissue adhesive may not be as effective in achieving optimal cosmesis for wounds on the forehead or of longer repair lengths. The majority of patients did not have a preference for wound closure techniques, but when a preference was given, cyanoacrylate was significantly favored over sutures. CONCLUSION: Cyanoacrylate tissue adhesive and fast absorbing gut suture both result in comparable aesthetic outcomes for epidermal closure of linear facial wounds following Mohs micrographic surgery. Consideration should be given to factors such as need for eversion, hemostasis, and wound tension when selecting an epidermal wound closure method. (ClinicalTrials.gov, Identifier: NCT01298167, http://clinicaltrials.gov/show/NCT01298167).

A comparative evaluation of oral hygiene practices, oral health status, and behavior between graduate and post-graduate dentists of North India: An epidemiological survey.

OBJECTIVES: The present study was carried out to compare oral hygiene practices, oral health status and behavior of graduate and postgraduate dentists of North India. MATERIALS AND METHODS: The study was carried out among 727 dentists (446 graduate i.e., Group A and 281 post graduate i.e., Group B) through an online questionnaire. The questionnaire covered oral hygiene regimen, adverse oral habits, information regarding dental visits and dental treatment. RESULTS: Results showed less than adequate oral hygiene practices among both the groups with more so in the graduate group (P ≤ 0.05). Very few dentists in both the groups reported any adverse oral habit. A more positive (P ≤ 0.05) attitude towards regular dental check up and dental treatment was seen in post-graduate dentists when compared to graduates. CONCLUSION: Very few dentists in both the groups followed ideal dental hygiene regimen. Dentists are the role models for the society as far as oral health is concerned; hence they need to be more responsible and lay more stress on their daily regimen and improve the scenario.