Evaluating Experimental, Knowledge-based and Computational Cocrystal Screening methods to advance Drug-Drug Cocrystal Fixed-dose Combination development.

Fixed-dose combinations (FDCs) offer significant advantages to patients and the pharmaceutical industry alike through improved dissolution profiles, synergistic effects and extended patent lifetimes. Identifying whether two active pharmaceutical ingredients have the potential to form a drug-drug cocrystal (DDC) or interact is an essential step in determining the most suitable type of FDC to formulate. The lack of coherent strategies to determine if two active pharmaceutical ingredients that can be co-administered can form a cocrystal, has significantly impacted DDC commercialisation. This review aims to accelerate the development of FDCs and DDCs by evaluating existing experimental, knowledge-based and computational cocrystal screening methods; the background of their development, their application in screening for cocrystals and DDCs, and their limitations are discussed. The evaluation provided in this review will act as a guide for selecting suitable screening methods to accelerate FDC development.

A Comprehensive Review of Challenges in Oral Drug Delivery Systems and Recent Advancements in Innovative Design Strategies.

The oral route of drug administration is often preferred by patients and healthcare providers due to its convenience, ease of use, non-invasiveness, and patient acceptance. However, traditional oral dosage forms have several limitations, including low bioavailability, limited drug loading capacity, and stability and storage issues, particularly with solutions and suspensions. Over the years, researchers have dedicated considerable effort to developing novel oral drug delivery systems to overcome these limitations. This review discusses various challenges associated with oral drug delivery systems, including biological, pharmaceutical, and physicochemical barriers. It also explores common delivery approaches, such as gastroretentive drug delivery, small intestine drug delivery, and colon-targeting drug delivery systems. Additionally, numerous strategies aimed at improving oral drug delivery efficiency are reviewed, including solid dispersion, absorption enhancers, lipidbased formulations, nanoparticles, polymer-based nanocarriers, liposomal formulations, microencapsulation, and micellar formulations. Furthermore, innovative approaches like orally disintegrating tablets (ODT), orally disintegrating films (ODF), layered tablets, micro particulates, self-nano emulsifying formulations (SNEF), and controlled release dosage forms are explored for their potential in enhancing oral drug delivery efficiency and promoting patients' compliance. Overall, this review highlights significant progress in addressing challenges in the pharmaceutical industry and clinical settings, offering novel approaches for the development of effective oral drug delivery systems.

Esophageal transit of solid oral dosage forms - impact of different surface materials characterized in vitro and in vivo by MRI in healthy volunteers.

Acceptable swallowability and complete esophageal transit are decisive for the safe and effective administration of solid oral dosage forms. This applies in particular to the main user group of medicines, older adults, who often suffer from swallowing difficulties. It is well known that surface properties play an important role in this respect. In the past, this has led to the development of numerous coating formulations for tablets with improved swallowability. However, in vitro and especially in vivo data investigating a positive effect of different coating materials is limited. Therefore, we investigated coating materials being based on polyvinyl alcohol, hydroxypropyl methylcellulose, and a copolymer of methacrylate in respect to their influence on swallowability and esophageal transit of a tablet formulation. They were compared to uncoated tablets as well as to hard gelatin capsules. Three in vitro assays suitable for routine use in pharmaceutical development were performed: i.) Wettability test in artificial saliva; ii.) Swelling measurement in artificial saliva; iii.) Measurement of the adhesion between surface materials and a simulated mucosa surface. All three assays resulted in a differentiation of the surface materials. The coated tablets showed favorable behavior compared to uncoated tablets and hard gelatin capsules. To test the effect of the different materials in vivo, an intervention study was conducted. 36 adults were included and the likeliness of prolonged esophageal transit of (un-)coated tablets as well as a hard gelatin capsule of the same weight was objectively evaluated by means of magnetic resonance imaging. While hard gelatin capsules showed highest rates for prolonged esophageal transit, the tendency for adhesion was reduced for uncoated tablets, and least for coated tablets, i.e., prolonged esophageal transit in 22.2%, 11.1%, and ≤5.6% of the cases, respectively. Further differentiation of the coating materials was not possible. Subjective evaluations of each participant with respect to subjective swallowability and esophageal transit did not correlate well with the objective measurements by means of magnetic resonance imaging. The use of coatings in general has a positive influence on esophageal transit. However, the selection of coating type seems to be of greater importance in respect to patients' oral perception of the dosage forms compared to their influence on the probability for prolonged esophageal transit.

Exploring Cationic Guar Gum: Innovative Hydrogels and Films for Enhanced Wound Healing.

Background/Objectives: This study developed and characterized hydrogels (HG-CGG) and films (F-CGG) based on cationic guar gum (CGG) for application in wound healing. Methods: HG-CGG (2% w/v) was prepared by gum thickening and evaluated for pH, stability, spreadability, and viscosity. F-CGG was obtained using an aqueous dispersion of CGG (6% w/v) and the solvent casting method. F-CGG was characterized for thickness, weight uniformity, morphology, mechanical properties, hydrophilicity, and swelling potential. Both formulations were evaluated for bioadhesive potential on intact and injured porcine skin, as well as antioxidant activity. F-CGG was further studied for biocompatibility using hemolysis and cell viability assays (L929 fibroblasts), and its wound-healing potential by the scratch assay. Results: HG-CGG showed adequate viscosity and spreadability profiles for wound coverage, but its bioadhesive strength was reduced on injured skin. In contrast, F-CGG maintained consistent bioadhesive strength regardless of skin condition (6554.14 ± 540.57 dyne/cm2 on injured skin), presenting appropriate mechanical properties (flexible, transparent, thin, and resistant) and a high swelling capacity (2032 ± 211% after 6 h). F-CGG demonstrated superior antioxidant potential compared to HG-CGG (20.50 mg/mL ABTS+ radical scavenging activity), in addition to exhibiting low hemolytic potential and no cytotoxicity to fibroblasts. F-CGG promoted the proliferation of L929 cells in vitro, supporting wound healing. Conclusions: Therefore, CGG proved to be a promising material for developing formulations with properties suitable for cutaneous use. F-CGG combines bioadhesion, antioxidant activity, biocompatibility, cell proliferation, and potential wound healing, making it promising for advanced wound treatment.

Developing Self-Nanoemulsifying Drug Delivery Systems Comprising an Artemether-Lumefantrine Fixed-Dose Combination to Treat Malaria.

BACKGROUND: Despite attempts to control malaria, poor drug bioavailability means malaria still places enormous pressure on health globally. It has been found that the solubility of highly lipophilic compounds can be enhanced through lipid formulations, e.g., self-emulsifying drug delivery systems (SEDDSs). Thus, quality-by-design and characterization were used to justify the development and determine the feasibility of oral oil-in-water SEDDSs comprising a fixed-dose combination (FDC) of artemether-lumefantrine to treat malaria more effectively without the aid of a fatty meal. These formulations were compared to a commercial product containing the same active compounds. METHODS: Excipient compatibility and spontaneous emulsification capacity of different FDC-excipient combinations were identified by employing isothermal microcalorimetry, solubility, and water titration tests. Pseudoternary phase diagrams were constructed, and checkpoint formulations were selected within the self-emulsification region by reviewing formulation properties essential for optimized drug delivery. SEDDSs capable of enduring phase separation within 24 h were subjected to characterization experiments, i.e., drug concentration determination, cloud point, droplet size, size distribution, self-emulsification time, self-emulsification efficacy, viscosity, zeta potential, and thermodynamic stability analysis. SEDDSs with favorable characteristics were identified in the micro or nano range (SNEDDSs) before being subjected to drug release studies. RESULTS: All final formulations depicted enhanced artemether and lumefantrine release compared to the commercial product, which could not release lumefantrine at a quantifiable concentration in this study. The avocado oil (AVO)4:6 and olive oil (OLV)3:7 SNEDDSs overall portrayed the ideal characteristics and depicted the highest percentage of drug release. CONCLUSIONS: This study offers evidence that SNEDDSs from selected natural oils comprising an artemether-lumefantrine FDC can potentially enhance the bioavailability of these lipophilic drugs.

Matrixing Designs for Shelf-Life Determination of Parenteral Drug Product: A Comparative Analysis of Full and Reduced Stability Testing Design.

This article highlights the applicability of matrixing designs in stability studies for parenteral medications. The traditional approach involves extensive testing over the product's shelf-life. However, matrixing designs offer an alternative approach where only a fraction of samples is tested at each time point. The study conducted in this article focused on three parenteral medications and examined stability data under long-term condition. Degradation products were identified as critical parameter, and kinetics of degradation varied among the selected products. A systematic methodology was adopted to evaluate the data using different matrixing designs. The regression models obtained were assessed using statistical parameters S and R2. Also, each of the 28 matrixing designs were compared to the full design with statistical parameter RMSE and the shelf-life. The results confirmed that each of the evaluated matrixing designs can be applied, whether degradation product shows a linear or non-linear increase, and demonstrated that a reduction of two time points per batch is the most appropriate. In conclusion, this research contributes to the understanding of utilizing reduced matrixing designs in stability studies for parenteral medications and can be an effective strategy to reduce costs and time of stability testing while maintaining the necessary level of precision and reliability.

Evaluation of floatability characteristics of gastroretentive tablets using VIS imaging with artificial neural networks.

Gastroretentive dosage forms are recommended for several active substances because it is often necessary for the drug to be released from the carrier system into the stomach over an extended period. Among gastroretentive dosage forms, floating tablets are a very popular pharmaceutical technology. In this study, it was investigated whether a rapid, nondestructive method can be used to characterize the floating properties of a tablet. To accomplish our objective, the same composition was compressed, and varied compression forces were applied to achieve the desired tablet. In addition to physical examinations, digital microscopic images of the tablets were captured and analyzed using image analysis techniques, allowing the investigation of the floatability of the dosage form. Image processing algorithms and artificial neural networks (ANNs) were utilized to classify the samples based on their strength and floatability. The input dataset consisted solely of the acquired images. It has been shown by our research that visible imaging coupled with pattern recognition neural networks is an efficient way to categorize these samples based on their floatability. Rapid and non-destructive digital imaging of tablet surfaces is facilitated by this method, offering insights into both crushing strength and floating properties.

Investigation of the State of Hydration of a Non-Stoichiometric Hydrate in a Low Dose Formulation Using 19F Solid-State NMR.

A variable or non-stoichiometric hydrate of GDC-4379 was developed into a formulated capsule with a 1% drug loading. The water content of this hydrate varied from 0-0.7 moles over the relative humidity (RH) range of 0-98% (25°C). Since a variable state of hydration coupled with rapid equilibration of lattice water with the environmental RH can lead to challenges in formulation development, an analytical method to directly and accurately determine the state of hydration of the active in such a low dose formulation was deemed necessary. Owing to its high selectivity and fast acquisition times, 19F solid-state NMR was effectively utilized to directly determine the lattice water content of the active in the formulated capsule. By correlating Δδ, the chemical shift difference between the isotropic peaks, with the relative humidity and ultimately the lattice water content, the state of hydration of GDC-4379 in the formulated capsule was experimentally determined as 0.63 moles of water/mole of anhydrate.

Selecting appropriate excipients for paediatric dosage form - Paediatric excipients risk assessment (PERA) framework - Part 1.

Excipients are often the major component of the formulation that critically affect the dosage form, manufacturing process, product performance, stability and safety. They exert different roles and functions in a dosage form. Selecting excipients with appropriate safety and tolerability is a major hurdle in paediatric formulation development. The suitability of a particular excipient will be dependent on the context of its use with regard to the paediatric age range, acute versus chronic use, and clinical risk-benefit of the disease, active and excipient. Scientists are encouraged to apply the principle of risk-benefit to assess the suitability of excipients to the specific paediatric population. Indicative list of parameters that should be taken into consideration and hierarchy of information sources when assessing the excipients risks is provided by regulatory agencies. However, the approach to be taken and details of how the risk evaluation should be undertaken are lacking. There is a need for a systematic approach to selection of excipients and assessment of the risk of excipient exposure. The Paediatric Excipients Risk Assessment (PERA) framework developed and proposed in this paper provides a structured, systematic decision-making framework via customizable tools and processes that can help to improve the transparency and communications on the selection and justification of use of excipients in a paediatric formulation.

A review of the physiological effects of microgravity and innovative formulation for space travelers.

During the space travel mission, astronauts' physiological and psychological behavior will alter, and they will start consuming terrestrial drug products. However, factors such as microgravity, radiation exposure, temperature, humidity, strong vibrations, space debris, and other issues encountered, the drug product undergo instability This instability combined with physiological changes will affect the shelf life and diminish the pharmacokinetic and pharmacodynamic profile of the drug product. Consequently, the physicochemical changes will produce a toxic degradation product and a lesser potency dosage form which may result in reduced or no therapeutic action, so the astronaut consumes an additional dose to remain healthy. On long-duration missions like Mars, the drug product cannot be replaced, and the astronaut may relay on the available medications. Sometimes, radiation-induced impurities in the drug product will cause severe problems for the astronaut. So, this review article highlights the current state of various space-related factors affecting the drug product and provides a comprehensive summary of the physiological changes which primarly focus on absorption, distribution, metabolism, and excretion (ADME). Along with that, we insist some of the strategies like novel formulations, space medicine manufacturing from plants, and 3D printed medicine for astronauts in longer-duration missions. Such developments are anticipated to significantly contribute to new developments with applications in both human space exploration and on terrestrial healthcare.

Full green assay of parenteral dosage forms of polymyxins utilizing xanthene dye: application to content uniformity testing.

Due to the lack of other treatment options, a rebirth of polymyxins is urgently required. Colistin (also called polymyxin E) and polymyxin B are the only two examples of this antibiotic class that were effectively employed in such critical situations. In the present work, both of the two studied medications were quantified via a simple, green, and non-extracting spectrophotometric approach based on the formation of ion-pair complexes with Erythrosine B. Without using any organic solvents, the pink color of the created complexes was detected at wavelength = 558 nm. To achieve the highest intensity of absorbance, optimum conditions were established by the screening of many experimental factors such as pH, buffer volume, the volume of Erythrosine B, and the time consumed to undergo the reaction. For Colistin and Polymyxin B respectively, Beer-Lambert's law was observed at the concentration ranges of 1-6, 1-9 µg mL- 1. The technique was approved and validated following ICH recommendations. Lastly, the suggested approach has been successfully implemented to quantify the cited medications colorimetrically, for the first time, in their parenteral dosage forms with excellent recoveries. Also, Content uniformity testing was implemented.

Manipulation of solid dosage forms for oral administration to paediatric patients for drug-resistant tuberculosis in South Africa: an observation study.

BACKGROUND: Children represent a particularly vulnerable demographic in the context of drug-resistant (DR) tuberculosis (TB) due to their increased likelihood of close contact with adults diagnosed with the disease. Approximately 25 000-30 000 children develop DR-TB annually. While treatment success rates for DR-TB in children surpass those in adults, children and adolescents encounter distinct challenges throughout the diagnosis and treatment of DR-TB (including MDR-TB, Pre-XDR TB, and XDR-TB). AIM: To identify current practices in drug administration to children diagnosed with DR-TB where appropriate dosage forms are not available in South Africa. METHOD: An observational study was carried out at the study site to determine how medication prescribed was manipulated and administered by nursing staff to paediatric patients in the wards. RESULTS: The observational study identified 8 drugs used in DR-TB at the study site, where some manipulation to the formulation was necessary to enable administration to paediatric patients. Linezolid and para-aminosalicylic acid are the only drugs available and registered in the South Africa in a formulation that is suitable for administration to paediatric patients. Activities carried out by nursing staff to enable the administration of DR-TB medication included cutting capsules and tablets and dissolving the tablet or capsule contents in distilled water to obtain the required suitable dose. DISCUSSION: Lack of availability of suitable dosage forms for paediatrics patients results in several challenges, such as additional time required for drug preparation, increased time duration of medication administration, and unpalatability of drugs. These challenges may subsequently affect compliance and therapeutic outcomes of the treatment of paediatric patients, especially as outpatients. CONCLUSION: Research needs to focus on the development of appropriate dosage forms for the paediatric population and focus on identifying cases of DR-TB in children. This will assist in building evidence to advocate for registration of child-friendly dosage forms thereby ensuring a sustainable supply of medication.

Characterization of Liquid Dosage Forms of Atenolol and Enalapril Maleate for Oral and Enteral Feeding Administration.

The limited availability of pharmaceutical formulations tailored for cardiovascular diseases in both pediatric and geriatric populations generates the need for compounded dosage forms to guarantee precise dosing and medication adherence. This study aimed to analyze the physicochemical properties and stability of formulations of atenolol and enalapril maleate prepared with a proprietary oral vehicle, SuspendIt®. To this end, palatability, injectability, pH, rheological behavior, and physical, microbiological, and chemical stability over a 180-day storage period at 25 °C and 5 °C were evaluated. Injectability tests confirmed the suitable use of both formulations for administration through enteral feeding tubes. By using a potentiometric electronic tongue, it was confirmed that the SuspendIt® vehicle effectively served as a bitter-blocking strategy for atenolol and enalapril maleate. Adequate stability throughout the storage period was confirmed in terms of the mechanical properties, pH, and effectiveness of the preservative system. The atenolol concentration remained above 90% of the initial amount, while the concentration of enalapril maleate decreased to 88% after 90 days of storage at 25 °C. In summary, the atenolol formulation maintained suitable chemical, physical, and microbiological stability after 180 days at both storage temperatures, while the enalapril maleate formulation remained stable up to 60 days at 25 °C and for 180 days at 5 °C.

Microfluidic Rheology: An Innovative Method for Viscosity Measurement of Gels and Various Pharmaceuticals.

Measuring the viscosity of pharmaceutical dosage forms is a crucial process. Viscosity provides information about the stability of the composition, the release rate of the drug, bioavailability, and, in the case of injectable drug formulations, even the force required for injection. However, measuring viscosity is a complex task with numerous challenges, especially for non-Newtonian materials, which include most pharmaceutical formulations, such as gels. Selecting the appropriate shear rate is critical. Since viscosity in many systems is highly temperature-dependent, stable temperature control is necessary during the measurement. Using microfluidics technology, it is now possible to perform rheological characterization and conduct fast and accurate measurements. Small sample volumes (even below 500 µL) are required, and viscosity determination can be carried out over a wide range of shear rates. Nevertheless, the pharmaceutical application of viscometers operating on the principle of microfluidics is not yet widespread. In our work, we compare the results of measurements taken with a microfluidic chip-based viscometer on different pharmaceutical forms (gels, solution) with those obtained using a traditional rotational viscometer, evaluating the relative advantages and disadvantages of the different methods. The microfluidics-based method enables time- and sample-efficient viscosity analysis of the examined pharmaceutical forms.

Stability of extemporaneously prepared hydroxyurea solutions.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To evaluate the stability of a new, more convenient (<30 minutes for preparation), extemporaneously prepared hydroxyurea solution over 78 days. METHODS: A high-performance liquid chromatography (HPLC) method using a hydrophilic interaction chromatography (HILIC) column was developed and validated to accurately measure the concentration of hydroxyurea directly from solution without the need for chemical derivatization. Hydroxyurea was dissolved in sterile water in less than 5 minutes to yield a 100-mg/mL solution, which was then diluted by an equal volume of ORA-sweet vehicle to yield a 50-mg/mL extemporaneously prepared solution of hydroxyurea. The solution samples were kept at refrigeration (4 °C), room temperature (26 °C), and elevated temperature (40 °C) for 78 days. RESULTS: The 50-mg/mL solutions of hydroxyurea in a 1:1 mixture of water and ORA-sweet kept at 4 °C and 26 °C showed no significant loss of potency (<2%) after 78 days. The solutions kept at 40 °C showed greater than 10% loss of potency after 28 days. CONCLUSION: Extemporaneously compounded hydroxyurea 50-mg/mL solutions prepared in a 1:1 mixture of water and ORA-Sweet and stored in amber polypropylene plastic bottles were stable for at least 78 days at room temperature and under refrigeration.

Development of novel antimicrobials with engineered endolysin LysECD7-SMAP to combat Gram-negative bacterial infections.

BACKGROUND: Among the non-traditional antibacterial agents in development, only a few targets critical Gram-negative bacteria such as carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii or cephalosporin-resistant Enterobacteriaceae. Endolysins and their genetically modified versions meet the World Health Organization criteria for innovation, have a novel mode of antibacterial action, no known bacterial cross-resistance, and are being intensively studied for application against Gram-negative pathogens. METHODS: The study presents a multidisciplinary approach, including genetic engineering of LysECD7-SMAP and production of recombinant endolysin, its analysis by crystal structure solution following molecular dynamics simulations and evaluation of antibacterial properties. Two types of antimicrobial dosage forms were formulated, resulting in lyophilized powder for injection and hydroxyethylcellulose gel for topical administration. Their efficacy was estimated in the treatment of sepsis, and pneumonia models in BALB/c mice, diabetes-associated wound infection in the leptin receptor-deficient db/db mice and infected burn wounds in rats. RESULTS: In this work, we investigate the application strategies of the engineered endolysin LysECD7-SMAP and its dosage forms evaluated in preclinical studies. The catalytic domain of the enzyme shares the conserved structure of endopeptidases containing a putative antimicrobial peptide at the C-terminus of polypeptide chain. The activity of endolysins has been demonstrated against a range of pathogens, such as Klebsiella pneumoniae, A. baumannii, P. aeruginosa, Staphylococcus haemolyticus, Achromobacter spp, Burkholderia cepacia complex and Haemophylus influenzae, including those with multidrug resistance. The efficacy of candidate dosage forms has been confirmed in in vivo studies. Some aspects of the interaction of LysECD7-SMAP with cell wall molecular targets are also discussed. CONCLUSIONS: Our studies demonstrate the potential of LysECD7-SMAP therapeutics for the systemic or topical treatment of infectious diseases caused by susceptible Gram-negative bacterial species and are critical to proceed LysECD7-SMAP-based antimicrobials trials to advanced stages.

The development of an innovative method to improve the dissolution performance of rivaroxaban.

Recent advancements in the formulation of solid dosage forms involving active ingredient-cyclodextrin complexes have garnered considerable attention in pharmaceutical research. While previous studies predominantly focused on incorporating these complexes into solid states, issues regarding incomplete inclusion prompted the exploration of novel methods. In this study, we aimed to develop an innovative approach to integrate liquid-state drug-cyclodextrin inclusion complexes into solid dosage forms. Our investigation centered on rivaroxaban, a hydrophobic compound practically insoluble in water, included in hydroxypropyl-ß-cyclodextrin at a 1:1 M ratio, and maintained in a liquid state. To enhance viscosity, hydroxypropyl-cellulose (2 % w/w) was introduced, and the resulting dispersion was sprayed onto the surface of cellulose pellets (CELLETS®780) using a Caleva Mini Coater. The process parameters were meticulously controlled, with atomization air pressure set at 1.1 atm and a fluidizing airflow maintained at 35-45 m3/h. Characterization of the coated cellets, alongside raw materials, was conducted using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) analyses. Physicochemical evaluations affirmed the successful incorporation of rivaroxaban into hydroxypropyl-ß-cyclodextrin, with the final cellets demonstrating excellent flowability, compressibility, and adequate hardness. Quantitative analysis via the HPLC-DAD method confirmed a drug loading of 10 mg rivaroxaban/750 mg coated cellets. In vitro dissolution studies were performed in two distinct media: 0.022 M sodium acetate buffer pH 4.5 with 0.2 % sodium dodecyl sulfate (mirroring compendial conditions for 10 mg rivaroxaban tablets), and 0.05 M phosphate buffer pH 6.8 without surfactants, compared to reference capsules and conventional tablet formulations. The experimental capsules exhibited similar release profiles to the commercial product, Xarelto® 10 mg, with enhanced dissolution rates observed within the initial 10 min. This research presents a significant advancement in the development of solid dosage forms incorporating liquid-state drug-cyclodextrin inclusion complexes, offering a promising avenue for improving drug delivery and bioavailability.

3D printed dosage forms, where are we headed?

INTRODUCTION: 3D Printing (3DP) is an innovative fabrication technology that has gained enormous popularity through its paradigm shifts in manufacturing in several disciplines, including healthcare. In this past decade, we have witnessed the impact of 3DP in drug product development. Almost 8 years after the first USFDA approval of the 3D printed tablet Levetiracetam (Spritam), the interest in 3DP for drug products is high. However, regulatory agencies have often questioned its large-scale industrial practicability, and 3DP drug approval/guidelines are yet to be streamlined. AREAS COVERED: In this review, major technologies involved with the fabrication of drug products are introduced along with the prospects of upcoming technologies, including AI (Artificial Intelligence). We have touched upon regulatory updates and discussed the burning limitations, which require immediate focus, illuminating status, and future perspectives on the near future of 3DP in the pharmaceutical field. EXPERT OPINION: 3DP offers significant advantages in rapid prototyping for drug products, which could be beneficial for personalizing patient-based pharmaceutical dispensing. It seems inevitable that the coming decades will be marked by exponential growth in personalization, and 3DP could be a paradigm-shifting asset for pharmaceutical professionals.

Liquid- and Semisolid-Filled Hard Gelatin Capsules Containing Alpha-Lipoic Acid as a Suitable Dosage Form for Compounding Medicines and Dietary Supplements.

Liquid-filled hard gelatin capsules may have pertinent advantages both for therapeutic effect and extemporaneous preparations of medicines. Alpha lipoic acid is a substance used in medicines and dietary supplements and there is a need for creating an appropriate formulation which would be suitable for each individual patient or consumer. Based on its biopharmaceutical and physical chemical characteristics, eight different capsule formulations were designed and characterized. Silicon dioxide was added to form a semisolid content and prevent leakage. The formulation filled with alpha lipoic acid solution in polyethylene glycol 400 showed the best performance. Although the addition of silicon dioxide to the formulation with polyethylene glycol 400 led to a change in both flow character and viscosity, the release rate did not show a statistically significant decrease (more than 85% of content was released after 5 min testing). Applied technique is a simple and an appropriate approach for compounding and could be used for other substances with similar properties.

Quantitative analysis of solid dosage forms of Atenolol by Raman spectroscopy.

OBJECTIVE: To develop a Raman spectroscopy-based analytical model for quantification of solid dosage forms of active pharmaceutical ingredient (API) of Atenolol.Significance: For the quantitative analysis of pharmaceutical drugs, Raman Spectroscopy is a reliable and fast detection method. As part of this study, Raman Spectroscopy is explored for the quantitative analysis of different concentrations of Atenolol. METHODS: Various solid-dosage forms of Atenolol were prepared by mixing API with excipients to form different solid-dosage formulations of Atenolol. Multivariate data analysis techniques, such as Principal Component Analysis (PCA) and Partial least square regression (PLSR) were used for the qualitative and quantitative analysis, respectively. RESULTS: As the concentration of the drug increased in formulation, the peak intensities of the distinctive Raman spectral characteristics associated with the API (Atenolol) gradually increased. Raman spectral data sets were classified using PCA due to their distinctive spectral characteristics. Additionally, a prediction model was built using PLSR analysis to assess the quantitative relationship between various API (Atenolol) concentrations and spectral features. With a goodness of fit value of 0.99, the root mean square errors of calibration (RMSEC) and prediction (RMSEP) were determined to be 1.0036 and 2.83 mg, respectively. The API content in the blind/unknown Atenolol formulation was determined as well using the PLSR model. CONCLUSIONS: Based on these results, Raman spectroscopy may be used to quickly and accurately analyze pharmaceutical samples and for their quantitative determination.