Dissolution Test Research Articles

Are Nanostructured Lipid Carriers (NLC) better than Solid Lipid Nanoparticles (SLN) for delivering abiraterone acetate through the gastrointestinal tract?

Abiraterone acetate (AbA) is a progesterone derivative indicated for the treatment of metastatic prostate cancer. This BCS (Biopharmaceutics Classification System) Class IV molecule has an extremely poor oral bioavailability (<10 %), notably due to its very low water solubility and intestinal permeability. Among the few existing galenic strategies to improve AbA’s oral bioavailability, lipid nanoparticles such as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are relevant nanovectors. The objective of this study is to develop and compare SLN and NLC for oral delivery of abiraterone acetate. Both SLN and NLC are biocompatible, biodegradable and produced by high pressure homogenization (HPH), an ecological-friendly manufacturing process, organic solvent-free and easily scalable. The HPH process allowed the formation of AbA-loaded SLN and NLC with particle size lower than 160 nm and high encapsulation efficiencies. The addition of a liquid lipid significantly reduced the mean diameter of the nanoparticles, reflecting the greater benefit of the NLC formulation compared to SLN. Both SLN and NLC formulations offered an important protection of AbA in intestinal media, with a better stability for NLC. When encapsulated in SLN or NLC, the AbA is strongly retained by the nanoparticles, whatever the dissolution medium, which means that both formulas are able to protect and retain the drug in the intestinal tract, right up to its delivery to the enterocytes surface. High concentrations of nanoparticles were administered without cytotoxicity, especially for the NLC, which provides a real added value in terms of biocompatibility with Caco-2 cells. Finally, the nanoparticles were able to penetrate into enterocytes by the transcellular route, demonstrating an intense cellular internalization.

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Voriconazole.

According to the ICH M9 Guideline, the triazole antifungal voriconazole is a Biopharmaceutics Classification System (BCS) class II drug, being highly soluble at the highest dose strength but not at the highest single dose. Although the ICH M9 allows for consideration of BCS-based biowaivers in such cases, voriconazole does not meet the additional requirement of dose proportional pharmacokinetics (PK) over the therapeutic dose range. By contrast, if the classification were based on the FDA solubility criteria that were in place prior to ICH M9 (based on the highest dose strength), voriconazole would belong to BCS class I and thus qualify for the BCS-based biowaiver. Since the highest oral dose strength of voriconazole dissolves very rapidly under all BCS conditions, and comparative in vitro dissolution of different tablet formulations aligns with the demonstration of BE in clinical studies, it seems that the ICH Guideline may be unnecessarily restrictive in the case of voriconazole. Therefore, this review discusses potential revisions of eligibility criteria and the extension of biowaiver approvals to encompass a wider range of appropriate drugs. Specifically, a classification system that is more relevant to in vivo conditions, the refined Developability Classification System (rDCS), coupled with biorelevant dissolution testing, may be more applicable to compounds like voriconazole.

Physico-Chemical Characterizations of Composited Calcium-Ortho-Phosphate Porous Particles and Their Controlled Release Behavior of Clindamycin Phosphate and Amikacin Sulfate

The porous particles prepared from composited calcium–ortho-phosphate (biphasic), Thai silk fibroin, gelatin, and alginate, with an organic to inorganic component ratio of 15.5:84.5, were tested for their abilities to control the release of the commercialized antibiotic solutions, clindamycin phosphate (CDP) and amikacin sulfate (AMK). The in vitro biodegradability tests complying to the ISO 10993-13:2010 standard showed that the particles degraded &lt;20 wt% within 56 days. The drugs were loaded through a simple adsorption, with the maximum loading of injection-graded drug solution of 43.41 wt% for CDP, and 39.08 wt% for AMK. The release profiles from dissolution tests of the drug-loaded particles varied based on the adsorption methods used. The drug-loaded particles (without a drying step) released the drug immediately, while the drying process after the drug loading resulted in the sustained-release capability of the particles. The model-fitting of drug release profiles showed the release driven by diffusion with the first-ordered kinetic after the initial burst release. The released CDF and AMK from particles could sustain the inhibition of Gram-positive bacteria and Gram-negative bacteria, respectively, for at least 72 h. These results indicated the potential of these composited particles as controlled-release carriers for CDP and AMK.

Pharmaceutical Equivalence of Film-Coated and Chewable Tablets: A Comparative Dissolution Study Using Pulverized Chewable Tablets

Famotidine is a histamine H2 receptor antagonist used in the treatment of gastrointestinal disorders. It is available in multiple formulations, including film-coated tablets, chewable tablets, oral suspension, and injections. The purpose of this study was to develop and evaluate the film-coated tablet (FT) containing famotidine, magnesium hydroxide, and precipitated calcium carbonate, designed to be pharmaceutically equivalent to the marketed chewable tablet (CT). To achieve the pharmaceutical equivalence of two tablets, the dissolution profiles of FT should be similar to those of CT. However, since CT is intended to be chewed before swallowing, testing it in its intact form would not provide accurate results. Therefore, pulverized chewable tablets (PCT) were used as the reference product. The dissolution, performed by the paddle method at 50 rpm, was analyzed by the validated UV method. Similarity factor (f2) and difference factor (f1) were calculated to assess the equivalence of the dissolution profiles. The results demonstrated that the dissolution profiles of the FT and CT were similar. Additionally, the acid-neutralizing capacity test confirmed the equivalence of the two antacids. This study is one of the first to propose that dissolution tests for pharmaceutical equivalence should be conducted on pulverized CTs when developing generic equivalents to CTs.

FORMULATION AND IN VITRO TESTS OF KETOPROFEN NANOSUSPENSION USING THE MILLING METHOD WITH POLYMER VARIATIONS

Objective: The aim of this research was to formulate ketoprofen nanosuspension with a variety of polymers and to compare the dissolution rate of the nanosuspensions with ketoprofen suspension. Methods: Ketoprofen nanosuspension was formulated by milling method using a different polymer such as Polyvinyl Pyrrolidone (PVP) K-30 (F1), Polyvinyl Alcohol (PVA) (F2) and Hydroxy Propyl Methyl Cellulose (HPMC) (F3). Nanosuspensions were prepared and characterized, including organoleptic, pH, particle size, zeta potential, Polydispersity Index (PI), specific gravity, crystalline state determination, physical stability at room temperature for 3 mo, and in vitro dissolution test compared with ketoprofen suspension. Results: The ketoprofen nanosuspensions with PVP K-30 and PVA showed stable preparations, while those with HPMC showed less stability, as indicated by sedimentation during storage. The particle size values of PVP K-30 and PVA were 10.004±0.03 nm; and 9.560±0.01 nm; zeta potential and polydispersity index values met the test requirements. The dissolution rate of the ketoprofen nanosuspensions was higher with a cumulative of F1, F2, and F3 were 83.35%; 85.00%, and 81.09% after 60 min, while the ketoprofen suspension was only 7.62%. Conclusion: The milling method of ketoprofen nanosuspensions with PVP and PVA has more stable physical characteristics than nanosuspension with HPMC. The ketoprofen nanosuspensions have a higher dissolution rate than the ketoprofen suspension.

Circulation of COVID-19-Related Medicines on Japanese Websites during the COVID-19 Pandemic and Their Quality and Authenticity.

Substandard and falsified medical products for treating COVID-19 have spread worldwide. These medicines have entered Japan through personal importation of products purchased via the Internet. In this study, we investigated the circulation of 19 COVID-19-related medicines on the Internet in Japan and evaluated the pharmaceutical quality and authenticity of 2 medicines (dexamethasone tablets and ivermectin tablets) obtained online. We purchased 23 samples of 0.5-mg dexamethasone tablets and 13 samples of 3-mg ivermectin tablets from the Internet in December 2020 and July 2022. We investigated the quality and authenticity of the obtained samples through visual observation and tested their authenticity. We conducted pharmacopoeia compliance testing (quantitative assay, content uniformity tests, and dissolution tests) using the high-performance liquid chromatography-photodiode array detector method. No prescription was ever required at the time of purchase. Visual observation revealed that most samples lacked a package insert and some samples had packaging deficiencies. In terms of authenticity, eight ivermectin samples were genuine; the authenticity of the other samples remained uncertain. Four dexamethasone samples and three ivermectin samples failed quality testing based on pharmacopeia validation standards. Our findings illustrate that dexamethasone and ivermectin tablets of poor quality are available online. It is important to increase consumer awareness and provide information about these medicines to prevent the purchase of substandard medicines via the Internet.

Comparison of dissolution profiles of brand name and generic drugs of mycophenolate mofetil in the presence of concomitant drugs

Generic drugs have become popular because they reduce medical costs. However, switching from a brand name drug to a generic drug of mycophenolate mofetil (MMF) in immunosuppressive therapy after kidney transplantation resulted in an insufficient increase in its blood concentration in some cases. Immunosuppressive therapy after transplantation typically involves a multidrug strategy. Therefore, changes in efficacy due to switching to a generic drug of MMF may be due to its combination with other drugs. Since the first barrier to the absorption of an orally administered formulation is dissolution, the present study examined the effects of prednisolone (PDN) and tacrolimus (TAC), which are used in immunosuppressive therapy, on the dissolution behavior of MMF. A dissolution experiment was performed in the 1st liquid for dissolution testing (pH 1.2), McIlvaine buffer (pH 4.0), and a 2nd liquid for dissolution testing (pH 6.8) under the single condition of the brand name drug and two generic drugs of MMF as well as under combined conditions with PDN and TAC. Although the initial dissolution rate of MMF differed between the brand name and generic drugs, no significant difference was observed in the final dissolution rate. Furthermore, the f2 value, which evaluates the equivalence of dissolution behavior, was within the standard range. In the 2nd liquid for dissolution testing (pH 6.8), the dissolution rate and ratio slightly decreased under the combined condition with PDN or TAC; however, in comparisons with the single conditions, the f2 value was within the standard range. Therefore, a reduced blood concentration due to switching to a generic drug of MMF may not be due to a change in dissolution behavior.

Effect of Fiber Cross-Sectional and Surface Properties on the Degradation of Biobased Polymers.

Biobased polymers such as polylactic acid (PLA) and polybutylene succinate (PBS) break down naturally under certain environmental conditions. The efficiency of degradation can be linked directly to fiber surface properties, which influence polymer accessibility. Here, the degradation of PLA and PBS fibers with six different cross-sections was investigated. The fibers were aged by hydrolysis and UV exposure in an accelerated weathering test, followed by an ISO 20200 laboratory-scale disintegration test with non-aged fibers as controls. The polymers were analyzed by differential scanning calorimetry, Fourier transform infrared spectroscopy, and gel permeation chromatography, comparing the polymer granulate, virgin fibers, and UV-exposed fibers. It was found that the molecular mass and crystallinity of PBS changed more than PLA during spinning. Several PLA samples were completely degraded, whereas all the PBS samples remained intact. Furthermore, surface openings appeared on the PLA fibers during weathering, suggesting greater sensitivity to UV exposure and hydrolysis than PBS. A clear correlation between the fiber surface area and the degradation rate was observed for all samples, but the correlation was positive for PLA and negative for PBS. The slower degradation of PBS fibers with a larger surface area may reflect the ability of PBS to preserve itself by further crystallization during degradation processes at temperatures higher than the glass transition point. The data clearly show that the analysis of single degradation mechanisms is insufficient to predict the behavior of material under real-world conditions, where different degradation mechanisms may work in parallel or consecutively, and may show interdependencies.

Formononetin-Loaded Self-Microemulsion Drug Delivery Systems for Improved Solubility and Oral Bioavailability: Fabrication, Characterization, In Vitro and In Vivo Evaluation.

This study aimed to construct a self-microemulsion drug delivery system (SMEDDS) for Formononetin (FMN) to improve its solubility and bioavailability while combining the nanocrystals (NCs) technology. The SMEDDS prescription composition was optimized with a pseudo-three-phase diagram, followed by a series of in vitro and in vivo evaluations of the selected optimal prescriptions. FMN-NCs loaded SMEDDS showed a homogeneous spherical shape in the Transmission electron microscope and the particle size was measured as (20.65 ± 1.42) nm. The in vitro cumulative release rate in each dissolution medium within 30min was higher than 80%, much higher than that of FMN (6%) and FMN-NCs (40%); Cellular experiments confirm that the formulation has a high safety profile and significantly promotes cellular uptake. The results of pharmacokinetics and intestinal absorption in rats showed that the relative bioavailability of FMN-NCs and FMN-NCs loaded SMEDDS were (154.80 ± 3.76)% and (557.73 ± 32.88)%, respectively, and both of them significantly increased the rate and extent of absorption of the drug in intestinal segments. FMN-NCs loaded SMEDDS significantly enhanced the solubility and bioavailability of FMN.

Counteracting the Loss of Release for Indomethacin-Copovidone ASDs

This work revisits the changing release behavior of indomethacin(IND)-copovidone amorphous solid dispersions (ASDs) when increasing their drug load (DL). While showing congruent release behavior at DL 0.1, ASDs with DLs of 0.3 and higher show incongruent release finally resulting in a complete loss of release. To study and explain this phenomenon, we modeled the release kinetics of these ASDs and looked into their phase behavior both experimentally and theoretically. We applied a diffusion model to accurately describe experimental release profiles for congruent release, incongruent release as well as for loss of release. Predicted concentration profiles for IND, copovidone, and water within the ASD revealed the formation of an ASD layer that almost exclusively contains amorphous IND. Our phase-diagram predictions and experimental data explain this phenomenon by water-induced phase separation in those parts of the ASD which did absorb water from the dissolution medium. Whereas the evolving copovidone-rich phase dissolved, the IND-rich phase remained undissolved and formed a super-hydrophobic cover of the remaining inner core of the ASD, thus finally completely preventing its dissolution. Higher DLs promote phase separation. This leads to the counterintuitive effect that the higher the DL, the lower the absolute amount of IND released. While the ASD containing 6 mg IND (DL 0.1) released 6 mg IND, the one containing 42 mg IND (DL 0.7) released only 1 mg IND. The theoretical approach applied in this work is for the first time able to quantitatively predict that reducing DL or tablet size could be used to overcome this problem.

Development and characterization of novel fast-dissolving pentobarbital suppositories for pediatric procedural sedation and comparison with lipophilic formulations

For pediatric radiological procedures (RP), pentobarbital sodium (PNa) can be used orally or rectally to replace intravenous anesthesia. Since no commercial PNa suppositories exist, they must be prepared by compounding pharmacies. This study aims to develop fast-dissolving PNa suppositories for fast pharmacological activity during RP. We prepared gelatin (G), gelatin/polyethylene glycol 4000 (GP), and polyethylene glycol 4000 (P) suppositories, with and without pH adjustment, and assessed their dosage uniformity (DU), softening time, rupture resistance, and in-vitro dissolution. An optimal formulation was selected, and PNa release was compared to that of fat-based suppositories using dissolution tests. Additionally, the quality control process (analytical performance, safety/eco-friendliness and productivity/practical effectiveness) of these formulas were compared using a RGB method. All hydrophilic formulas (HF) met the DU requirement (AV < 8 %) except for P (AV 15.62 ± 4 %). pH adjustment enhanced G and GP suppositories resistance to 2.2 ± 0.2 kg and 2.0 ± 0.3 kg, respectively, and allowed 100 % release of PNa in under 10 min. In contrast, lipophilic formulas released less than 80 % of PNa at best after 120 min. These results show the biopharmaceutical suitability of HF for RP compared to lipophilic ones, but a pharmacokinetic study is needed to confirm data.

Novel 3D printed capsule to work as an auxiliary for enteric-coating for gastroprotective drug delivery system.

In the current research work, 3d printed capsules were printed by using FDM based 3D printer. A model drug punched into matrix tablets was put inside and encapsulated in the capsule. It was compared with the highly advanced ready-to-fill enteric-coated capsule Eudracap™ capsule. Solid Works and slicing software were used to design and cast off the shape of the capsule shell. The design of the cap and body was made and capsules were printed accordingly. All were evaluated for acid uptake and disintegration tests. In an acidic medium at pH 1.2, it has not been disintegrated or opened. While in the intestinal pH at 6.8 body and cap got separated after 45 ± 05 min. All sizes of capsules were also assessed for dosage form they can uphold. This could be a good option for customized drug delivery for human and animal studies.

Strap-on Buoyant Device to Enhance Gastrointestinal Tract Retention of Felodipine Osmotic Pump Tablets.

Osmotic pump systems require prolonged retention time in the stomach to provide enhanced bioavailability and regulated release, which is quite challenging. This study used a three-dimensional printing (3DP) technique combined with a gastro-retentive floating device (GRFD) to extend the retention of the osmotic pump in the stomach and enhance its bioavailability. The strap-on buoyant device was fabricated by stereolithography 3DP and incorporated a felodipine osmotic pump tablet used in clinical practice, which enabled it to float in the stomach or dissolution media without any floating lag time. The components of the device were affixed using a snap-fix mechanism. GRFD dissolution study revealed a notable in vitro floating capability, lasting over 24h, with a release profile similarity factor f2 = 65.28 compared to the naked tablet dissolution profile. The pharmacokinetics of felodipine osmotic pump in beagles showed a Cmax of 1.893 ng/mL, which increased to 4.511 ng/mL with GRFD. The delivery of an osmotic pump with GRFD enhanced the AUC0-∞ of felodipine from 10.20 ng/mL·h to 26.54 ng/mL·h. In conclusion, the strap-on buoyant device has been successfully designed to enhance gastrointestinal tract retention of felodipine osmotic pumps and bioavailability in beagles.

Development of 3D-Printed Two-Compartment Capsular Devices for Pulsatile Release of Peptide and Permeation Enhancer.

The oral absorption of a peptide is driven by a high local concentration of a permeation enhancer (PE) in the gastrointestinal tract. We hypothesized that a controlled release of both PE and peptide from a solid formulation, capable of maintaining an effective co-localized concentration of PE and peptide could enhance oral peptide absorption. In this study, we aimed to develop a 3D-printed two-compartment capsular device with controlled pulsatile release of peptide and sodium caprate (C10). 3D-printed two-compartment capsular device was fabricated using a fused deposition modeling method. This device was then filled with LY peptide and C10. The release profile was modulated by changing the thickness and polymer type of the capsular device. USP apparatus II dissolution test was used to evaluate the impacts of device thickness and polymer selection on release profile in vitro. An optimal device was then enteric coated with HPMCAS. A strong linear relationship between the thickness of capsular devices and the delay in the release onset time was observed. An increase in the device thickness or the use of PLA decreased the release rate. The capsular device with compartment 1, compartment 2 and fence thickness of 0.4; 0.95 and 0.5mm, respectively, and the use of PVA achieved desired pulsatile release profiles of both peptide and C10. Furthermore, enteric-coated capsular devices with HPMCAS had similar pulsatile release profiles compared to non-enteric coated devices. These findings suggest potential application of 3D-printing techniques in the formulation development for complex modified drug release products.

Pharmaceutical availability testing − can a drug-specific test be relevant for assessing the quality of dietary supplements?

Our current novel analytical approach focuses on testing the quality of dietary supplements. Specifically, we examine the release of substances such as proline, tryptophan, tyrosine, carnitine, and vitamin C sourced from the EU, Switzerland, and the USA.In tablet-form supplements, release levels were low in both pharmacopoeial dissolution tests (Trp5 – 23%; Trp6 – 12%; VitC4 – 23%) and those simulating biorelevant conditions (Trp5 – 53%; Trp6 – 24%; VitC4 – 68%). The implementation of biorelevant conditions PhysioCell for capsule-form supplements led to an enhanced release of substances (from 11 to 106 percentage points) compared to pharmacopoeial dissolution tests. This indicates that the release of their active substance is strongly influenced by gastrointestinal motility, which, due to its high intra- and inter-individual variability, will result in inconsistent and unpredictable release and biological response.Thus, pharmacopeial methods serves as a reliable screening approach for the quality of dietary supplements.

Preparation and evaluation of soft gelatin capsules loaded with astaxanthin, niacin and garlic oil for removal of plague in atherosclerosis

Atherosclerosis, a chronic inflammatory disease, is the leading cause of cardiovascular diseases. In atherosclerosis, the arterial walls are characterized by plaque deposits on the inside of arteries. This study focuses on preparing a fill formulation to remove plaque in atherosclerosis, then analyse the pharmaceutical ingredients used and later produce soft gelatin capsules. Soft gelatin capsules are hermetically sealed, one-piece capsule which has a suspension or semi-solid as fill. Oxidative stress and inflammation are factors responsible for the development of atherosclerosis. Hence, the active pharmaceutical ingredients (APIs) chosen for fill formulation need to possess effective anti-oxidant and anti-inflammatory properties. A novel combination of APIs: Astaxanthin, Niacin and Garlic oil were chosen for the removal of plaque in atherosclerosis. Each of these APIs is known to possess a specific function in the control of plaque development. The fill formulation prepared was analysed for its recovery using various analytical techniques like UV spectrophotometry, high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). This fill formulation was encapsulated within the gelatin shell prepared to produce soft gelatin capsules. The encapsulated soft gelatin capsules were evaluated based on various parameters which include average net weight, disintegration test, loss on drying and dissolution.

Development and characterisation of orally disintegrating flurbiprofen tablets using SeDeM-ODT tool.

In this study, SeDeM-ODT parametric tests were performed to determine the use of ludipress as a directly compressible tableting excipient for the development of a flurbiprofen orally disintegrating tablet. The preformulation features of different formulations (F1 -F9) were analyzed by the SeDeM-ODT tool which showed that all the powder blends were appropriate for direct compression since all the blends had index of good compressibility and bucodispersibility (IGCB) values above 5, signifying direct compression is the most appropriate method. The powder blend of the optimized formulation was assessed by the DSC-TGA technique. The optimization of nine different formulations blends of orally disintegrating tablets (ODTs) was prepared in various ratios by the implementation of design of experiments (DoE), using the central composite design by selecting ludipress (X1) (49-55%) and croscarmellose sodium (X2) (1-5%) while hardness, friability, and disintegration tests were selected as responses. The optimized formulations were evaluated by various tests and the results indicated that all the formulations were found to be in adequate range. Formulations were subjected to stability studies at accelerated states following ICH guidelines. Shelf life was found to be 51.144-56.186 months. Results of multiple-point dissolution studies revealed that formulations followed the Higuchi kinetic model. This study revealed that the SeDeM-ODT tool has been successfully used to determine the compression behavior of active compounds and their powder blends for the direct compression (DC) method in formulating flurbiprofen-ODT tablets.

Enhancing the In vivo Bioavailability and Absorption of Niclosamide with Amorphous Solid Dispersion via Solvent Method

Abstract Objective This research aims to prepare a superior amorphous solid dispersion (ASD) formulation via solvent method for the oral delivery of Niclosamide to enhance oral bioavailability and absorption. Methods Phase solubility tests were conducted to select an optimal carrier combination for Niclosamide solid dispersion (SD). The Niclosamide amorphous solid dispersion was synthesized using a solvent rotary evaporation method and characterized through in vitro dissolution tests, differential scanning calorimetry (DSC), modulated DSC, powder X-ray diffraction, and scanning electron microscopy. In vivo oral pharmacokinetic studies were conducted in in Sprague Dawley rats at a dose of 50 mg/kg. Key findings PEG6000 and poloxamer 188 combination was selected as optimal carrier. ASD named ASD-5 was successfully prepared, encompassing a 25% drug loading, Niclosamide within ASD-5 remains amorphous and stable. 75% of Niclosamide in ASD-5 rapidly dissolved in 5 min, while below 5% of pure Niclosamide and physical mixture dissolved in longer time. Amorphization of Niclosamide in ASD-5 notably contributes to its dissolution rate and extent. Furthermore, among reported Niclosamide solid dispersion formulations with drug loading above 25%, ASD-5 demonstrated the highest bioavailability, showing a 2.33-fold increase in plasma exposure and bioavailability compared to pure Niclosamide. Conclusion Amorphous ASD-5 prepared by solvent method has higher drug loading and be scalable in pre-clinical stage preparation. Due to using PEG6000 and poloxamer 188 combination, ASD-5 had the highest bioavailability among reported Niclosamide solid dispersions with a drug load exceeding 25%. Also, ASD-5 presented simplified preparation procedure compared to other reported Niclosamide solid dispersion.

NIR-Guided Coating Optimization of Omega-3 Fatty Acid Mini Soft Capsules with Pitavastatin and Ezetimibe

Background: This study aimed to optimize the coating process of Omega-3 fatty acid (OM3-FA) mini soft capsules containing the active pharmaceutical ingredients (APIs) pitavastatin and ezetimibe using near-infrared (NIR) spectroscopy for in-process monitoring. Cardiovascular disease treatments benefit from combining OM3-FA with lipid-lowering agents, but formulating such combinations in mini soft capsules presents challenges in maintaining stability and mechanical integrity. Methods: The coating process was developed using a pan coater and real-time NIR monitoring to ensure uniformity and quality. NIR spectroscopy enabled precise control of coating thickness, ensuring consistent drug distribution across the capsule surface. Results: The optimized process minimized OM3-FA oxidation and preserved the mechanical integrity of the capsules, as confirmed by texture analysis and in-vitro dissolution testing. This integration of NIR spectroscopy as a process analytical technology (PAT) significantly improved coating quality control, resulting in a stable and effective combination therapy for pitavastatin and ezetimibe in a mini soft capsule form. Conclusion: This approach offers an efficient solution for enhancing patient adherence in cardiovascular disease management. The application of NIR spectroscopy for real-time monitoring highlights its broader significance in pharmaceutical manufacturing, where it can serve as a versatile tool for ensuring product quality and optimizing production efficiency in diverse formulation processes. By incorporating NIR-based PAT, manufacturers can not only achieve product-specific improvements but also establish a foundation for continuous manufacturing and automated quality assurance systems, ultimately contributing to a more streamlined and robust production environment.

The role of coatings and plasticizers compatibility in stability of advanced gastro-resistant self-emulsifying pellets designed for the delivery of volatile compounds: A combined solid-state NMR and dissolution study

The gastro-resistant behaviour of solid self-emulsifying drug delivery systems (S-SEDDS) represents a significant and innovative advancement in delivering poorly soluble drugs. Due to the complexity of these systems and the liquid nature of SEDDS, thorough investigation is essential. This study explored the stability of self-emulsifying (SE) pellets containing the volatile compound thymol coated with gastro-resistant Eudragit® L 30 D-55 water dispersion. The SE pellet cores, composed of Neusilin® US2 with adsorbed SEDDS (thymol, triacylglycerol, Labrasol®, and propylene glycol), microcrystalline cellulose, and chitosan, were prepared using the extrusion/spheronization method and demonstrated optimal technological properties. The 6-month stability of three coating compositions, differing in thickness and triethyl citrate (TEC) concentration in the Eudragit® L topcoat, or the application of an ethylcellulose (EC, Surelease®) sub-coat, was investigated using the combined in vitro dissolution testing and solid-state nuclear magnetic resonance (ss-NMR) for detailed structural characterization. The dissolution data of samples with Eudragit® L topcoat data showed an acceleration of thymol release in acidic conditions, preventing the SE pellets from achieving gastro-resistance. The ss-NMR analysis revealed an incompatibility between TEC and SEDDS (specifically propylene glycol), identified as a TEC phase transition to a liquid phase independent of TEC concentration. Additionally, ss-NMR analysis revealed that neat thymol negatively affected coating layer stability by promoting the plasticization of Eudragit® L. The inclusion of a 10 % Surelease® sub-coat yielded positive results, maintaining the gastro-resistant properties of SE pellets stored under 25 °C/60 % RH for 6 months. However, ss-NMR analysis confirmed ongoing TEC liquefaction after 3 and 6 months, indicating that the oleic acid and triglycerides in Surelease® as plasticizers contributed to this instability. Therefore, this formulation cannot be deemed stable, and using Surelease® as a sub-layer is only a temporary solution. Overall, while plasticizers are commonly used in pharmaceutical technology, they can introduce significant problems in S-SEDDS development, and their use in sub- or topcoats should be carefully considered or avoided. At the same time, it became evident that in-vitro dissolution testing alone cannot capture the slow processes and interactions occurring within the internal structure of these systems.