Dissolution Studies Research Articles

Formulation and Evaluation of Colon Specific Meloxicam Microcapsules for the Treatment of Arthritis

Objective: The main objective of the current study was to formulate and evaluate meloxicam-loaded microcapsules for colon-specific drug delivery using pH-dependent polymers. The emerging need for developing sustained release NSAIDs to minimize the dosing frequency was the main concern. Consequently, creating an oral sustained release formulation for the treatment of arthritis may be one method to get around this. Methods: Eudragit RS/RL-100 polymers were used in emulsion solvent evaporation processes to create Meloxicam (MLX) microcapsules. Compatibility tests (FTIR), surface morphology by Scanning Electron Microscopy (SEM), yield, drug content, entrapment efficiency, and in vitro dissolution studies were performed on the produced MLX microcapsules. Results: There was no interaction between the polymer and MLX, according to the IR spectra. The microcapsules were spherical in nature, which was confirmed by SEM. Normal frequency distribution MLX microcapsules were produced. The maximum drug entrapment efficiency of 94% was attained. The in vitro performance of MLX microcapsules demonstrated that the polymer concentration influenced sustained release. Furthermore, it was observed that the amount of polymer utilized regulated the release of the drug. Conclusion: Based on the findings, it was concluded that one of the most promising formulation methods for creating colon specific drug delivery systems for the treatment of arthritis is the production of MLX microcapsules.

DEVELOPMENT AND EVALUATION OF CYCLODEXTRIN NANOSPONGES-BASED TOPICAL FORMULATION OF TAZAROTENE

Objective: Tazarotene is used as a topical retinoid for the treatment of acne, psoriasis and sun-damaged skin. But its topical formulation has many side effects, including itching, burning, dryness, redness, stinging, rash blistering, skin discoloration, peeling at the site of application and low bioavailability. The present study focuses on the reduction of side effects and enhancement of solubility and topical bioavailability of tazarotene by using cyclodextrin-based nanosponges. Methods: Nanosponge of tazarotene were prepared by lyophilization method. The physiochemical characterization of plain nanosponges and drug-loaded nanosponges were performed using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-ray Diffractometer (XRD) studies. The drug-loaded nanosponges were incorporated into a carpool-based gel formulation. The prepared formulation was evaluated for viscosity, dissolution and stability. FTIR, DSC and XRD studies confirmed the formation of inclusion complex of tazarotene with nanosponges. Results: The particle size of the drug-loaded nanosponges was found to be in the range of 156.72 to 163.48 nm. Transmission Electron Microscopy (TEM) images revealed the regular spherical shape of both the nanosponges that are unaffected even after drug encapsulation. The pH of the gel formulations was found to be in the range of 5.86 to 6.46. The gel formulation resulted in the diffusion of drug in controlled manner for up to 24 h. The in vitro dissolution studies revealed that nanosponges-based topical formulation had better results than the marketed product. Conclusion: Thus, the study showed that nanosponge-based gel formulation can be a possible alternative to conventional formulations of tazarotene with enhanced bioavailability and skin retention characteristics for topical application.

Comparative Dissolution Study of Ciprofloxacin Hydrochloride-sustained Release Tablets by Using Carbopol-934 and Guar Gum Polymers

Aims: This study aimed to identify the potential release of the drug from the tablet dosage form using Carbopol-934 and Guar Gum polymers at different concentration ratios. Objective: The objective of this study was to determine the cumulative percentage of ciprofloxacin hydrochloride released from different polymers. Method: We formulated ciprofloxacin hydrochloride sustained-release tablets with Carbopol-934 and Guar gum using the wet granulation method. For the formulation of sustained-release ciprofloxacin hydrochloride tablets, both polymers were mixed in varying ratios. The tablets were examined for pre-formulation studies, including the angle of repose, bulk density, compressibility index, and physiological properties, such as variations in weight, friability, and drug content. For postformulation studies, such as the in vitro study, the in vitro release of the drugs was evaluated in a phosphate buffer solution (pH 7.4) for 8 h. However, the physiological properties of ciprofloxacin hydrochloride tablets were limited due to their liberality. Results: The tablets containing guar gum (Batches B-I and B-II) showed better drug content than other polymer-based batches, such as Carbopol-934 (Batch A-I, A-II) and a mixture of both polymer Carbopol-934 and Guar gum (Batch C-I, C-II). Sustained drug release was observed in the guar gum polymer-based tablets (Batch B-II). It was observed that the dissolution profile of ciprofloxacin hydrochloride tablets formed using different polymers showed an increase in the polymer ratio, which can be related to the increase in drug release. Conclusion: From this study, we can conclude that the ciprofloxacin hydrochloride drug release percentage was maximum when guar gum polymer was used in the tablet dosage form.

Development, Analysis, and Determination of Pharmacokinetic Properties of a Solid SMEDDS of Voriconazole for Enhanced Antifungal Therapy

Background: Voriconazole is an antifungal drug, which is classified under Bio-Classification System-II and has low water solubility (0.71 mg/mL) and high permeability. Hardly any endeavors have been made to increase the bioavailability of voriconazole. Objective: To develop and evaluate a solid SMEDDS (self-microemulsifying drug delivery system) for antifungal activity. Methods: Based on solubility studies of Labrafil-M 1994 CS (oil), Cremophor-RH 40 (a surfactant) and Transcutol-HP (a co-surfactant) were selected as components of the SMEDDS and a pseudo-ternary phase diagram was prepared. Thereafter, the oil, surfactant, and co-surfactant were mixed with altered weight ratios (1:1/1:2/2:1) and evaluated through various in vitro, in vivo analyses. Results: The particle size of the optimized formulation was observed to be 19.04 nm and the polydispersity index (PDI) value was found to be 0.162 with steady-state zeta potential. The optimized liquid SMEDDS was converted into a solid SMEDDS. Various adsorbents, such as Aerosil-200, Avicel-PH101, Neusilin-US2, and Neusilin UFL2 were screened to better detect the oil-absorbing capacity and flow properties of the powder. Neusilin UFL2 was selected as an adsorbent due to its better oil-absorbing capacity. DSC, X-ray diffraction, and dissolution studies were carried out to characterize the formulation. Further, the Pharmacokinetic profile was also studied in Wistar rats and the Cmax, tmax, and AUC0®t were calculated. The Cmax and AUC0®t plasma concentration is considerably better for the SMEDDS than for the pure drug and marketed formulation. Conclusions: This investigation clearly reveals the potential of developing a solid SMEDDS for candidiasis and invasive aspergillosis treatment, with better efficacy as compared to the commercially available marketed formulation.

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.

Evaluating Various Lactose Types as Solid Carriers for Improving Curcumin Solubility in Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDSs) for Oral Administration

Curcumin, a bioactive compound derived from turmeric, possesses numerous pharmaceutical properties; however, its poor aqueous solubility and permeability result in low bioavailability. This study aims to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) using different lactose types as solid carriers for the oral administration of curcumin to enhance its solubility. The system comprised curcumin, an oil phase, and a surfactant. Jasmine oil, as the oil phase, and Cremophor® RH40, as the surfactant, were selected due to their superior ability to solubilize curcumin. A microemulsion was then prepared using a ternary phase diagram. The liquid SNEDDSs were converted into S-SNEDDSs by employing three solid carriers: Tablettose® 80, FlowLac® 100, and GranuLac® 200. Dissolution studies conducted in simulated gastric fluid demonstrated a significant improvement in curcumin solubility in the S-SNEDDS formulations compared to curcumin powder. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses confirmed the appearance of curcumin in the S-SNEDDS, while Fourier-transform infrared (FTIR) spectroscopy indicated compatibility between the excipients and curcumin. Additionally, an accelerated stability study conducted over four weeks at 40 °C and 75% relative humidity showed no significant changes in the physical appearance of the S-SNEDDS formulations. These findings suggest that the S-SNEDDS formulation effectively enhances curcumin’s solubility, potentially improving its bioavailability for oral administration.

Extrusion-Based Three-Dimensional Printing of Metronidazole Immediate Release Tablets: Impact of Processing Parameters and in Vitro Evaluation

PurposeThe current study assessed the potential of a pneumatic 3D printer in developing a taste-masked tablet in a single step. Metronidazole (MTZ) was chosen as the model drug, and Eudragit® E PO was used as a taste-masking polymer to produce taste-masked tablets.MethodsThe study focused on optimizing processing parameters, such as the nozzle's printing speed, the printhead's heating temperature, and the pressure. Oval-shaped tablets were printed with a rectilinear printing pattern of 30% and 100% infill and evaluated for in vitro drug release and taste masking. The 3D-printed tablets are also characterized using Differential Scanning Calorimetry (DSC), Fourier-transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM).ResultsThe infill density impacts the drug release profile of the tablets. F9, F10, and F11 displayed desired printability among the formulations, with F9 and F10 exhibiting over 85% drug release within 60 min in the in vitro dissolution study. The F9 formulation, with 30% infill, effectively masked the bitter taste of MTZ in the in vitro dissolution study carried out in a pH 6.8 artificial salivary medium. The observed release was below the tasting threshold concentration of the model drug.ConclusionIn summary, 3-dimensional extrusion-based printing combines the effects of hot-melt extrusion and fused deposition modeling techniques in a single-step process, demonstrating potential as an alternative to the fused-deposition model 3D printing technique and warranting further exploration.Graphical

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.

Implementing the Design of Experiments (DoE) Concept into the Development of Mucoadhesive Tablets Containing Orange Peel Extract as a Potential Concept for the Treatment of Oral Infections

This study explores for the first time the impact of chitosan (CS) with varying molecular weights (MW), orange peel extract concentration, and hydroxypropyl methylcellulose (HPMC) content on the formulation of buccal tablets for treating oral infections. Utilizing a statistical design of experiments (DoE), nine different formulations were evaluated for mechanical properties, dissolution behavior, mucoadhesion, and biological activity. A formulation with high CS MW, 60% orange peel extract, and 8% HPMC, emerged as the optimal formulation, demonstrating superior tabletability, compressibility, and compactibility. Dissolution studies indicated that hesperidin release followed the Higuchi model, with higher extract content enhancing this phenomenon. Mucoadhesion improved with increased HPMC and CS concentrations, although higher extract content reduced bioadhesion. Biological assays showed that higher extract levels boosted antioxidant activity, while CS primarily contributed to anti-inflammatory effects. The optimized formulation exhibited broad antimicrobial activity against key oral pathogens, surpassing the effectiveness of the individual components. Principal component analysis (PCA) further confirmed the significant influence of extract content on tablet properties. These findings suggest that the optimized tablet formulation holds promise for effective buccal delivery in the treatment of oral infections, warranting further investigation in clinical settings.

Optimized freeze-dried solid-dispersions boost naringin solubility, antibacterial and in-vitro anticancer activity

Naringin (NRG) is a water insoluble glycoside having wide range of therapeutic efficacy. Its efficacy is limited due to its poor water solubility and bioavailability. In the current research, solid dispersions (SDs) were prepared by freeze drying method using different carriers KollidonVA64, KollidonVA30, Soluplus and Poloxamer188. The prepared binary SDs were characterized for solubility and dissolution study to select the optimized composition and further ternary SDs was prepared with carrier blend (KollidonVA64 and Soluplus). Finally, the ternary SDs (F6) was evaluated for solid state characterization (DSC, XRD, SEM), drug polymer interaction (IR), in vitro antioxidant, antimicrobial as well as cell viability study against neuroblastoma cell. The binary SDs developed with KollidonVA64 and Soluplus showed greater solubility than KollidonVA30 and Poloxamer188. The ternary SDs (F6), showed a significant enhancement in the saturation solubility and dissolution than binary SDs (F1-F4). The binary SDs (F1-F4) displayed the maximum release in 120 min (73.5±2.8 to 94.6±3.1%), whereas the ternary SDs (F6) showed the maximum release in 60 min (99.2±1.6%). The spectroscopy results confirm the formation of a stable dispersion and no drug polymer interaction was observed. The thermogram, diffractogram and microscopic image confirms the conversion of crystalline NRG to amorphous form. These findings support the results of saturation solubility and dissolution data. The in vitro antioxidant, antimicrobial and cytotoxicity assessment displayed a greater activity of developed NRG SDs than the free NRG. The enhancement in the results may be due to the enhanced solubility of NRG after formation of SDs using the KollidonVA64 and Soluplus carrier blend.

Screening of Polymers for Oral Ritonavir Amorphous Solid Dispersions by Film Casting

Background/Objectives: Drug–polymer interactions and miscibility promote the formation and performance of amorphous solid dispersions (ASDs) of poorly soluble drugs for improved oral bioavailability. The objective of this study was to employ drug–polymer interaction calculations and small-scale experimental characterization to screen polymers for potential ASDs of ritonavir. Methods: Seven polymers across four polymer types were screened as follows: an enteric one (EudragitS100), amphiphilic ones (HPMCAS-L, HPMCAS-H, and their 1:1 combination), hydrophilic ones (PEG-6000, PVP-VA), and a surfactant (Soluplus), including PVP-VA as a positive control, as the commercial ASD employs PVP-VA. Drug–polymer interaction calculations were performed for Hansen solubility parameter, Flory–Huggins parameter, and glass transition temperature. ASDs were prepared via film casting. Experimental characterizations included drug solubility in polymer solutions, polymer inhibition of drug precipitation, polarized light microscopy, differential scanning calorimetry, solubilization capacity, and dissolution studies. Results: HPMCAS-L, HPMCAS L:H, and Soluplus, along with the positive control PVP-VA, were identified as polymers for potential ASDs of ritonavir, with HPMCAS-L and PVP-VA being preferable. HPMCAS-L and the positive control PVP-VA were always viable for both 20% and 40% drug loads across all tests. Films with each of these four polymers showed improved dissolution compared to amorphous ritonavir without polymer. Drug–polymer interaction calculations anticipated the unfavorable small-scale experimental results for PEG-6000 and EudragitS100. Conclusion: Overall, the results contribute towards a resource-sparing approach to identify polymers for ASDs.

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.

Enhancing Ketoprofen Solubility: A Strategic Approach Using Solid Dispersion and Response Surface Methodology.

In the pharmaceutical sciences, the solubility profile of therapeutic molecules is crucial for identifying and formulating drugs and evaluating their quality across the drug discovery pipeline based on factors like oral bioavailability, metabolic transformation, biodistribution kinetics, and potential toxicological implications. The investigation aims to enhance the solubility parameters of ketoprofen (BCS-II class), which exhibits low solubility and high permeability. In this method, hydrotrope blends of aromatic sodium benzoate and electrolyte sodium acetate were employed to enhance the solubility parameter of ketoprofen. Several batches of solid dispersion of ketoprofen were made using a solvent evaporation method, and the response surface method 3² factorial design was used to find the best one. The optimised formulation, KSD9, underwent in-vitro drug dissolution, DSC, pXRD, and SEM studies. The optimized batch demonstrated substantial improvement in ketoprofen solubility, attributed to mixed hydrotropy. The results indicated that both solubility and %CDR improved when hydrotropes were employed, suggesting a direct proportionality between the rise in solubility and %CDR. Formulations KSD1-KSD9 exhibited solubility enhancements ranging from 2.23 to 5.77-fold, along with an elevation in %CDR from 72.28% to 94.76%. This implies that the %CDR was modulated by the hydrotropes, specifically influenced by the concentration levels of the independent variables. An increase in hydrotrope levels corresponded to an increase in %CDR. The positive coefficients in the quadratic equation for %CDR underscored the significant role of these independent variables in augmenting the in-vitro release of Ketoprofen. Similarly, during a comparative dissolution investigation, the optimized KSD9 formulation exhibited remarkable solubility and drug content compared to conventional Ketoprofen dispersible tablets. The synergistic effect of combining two hydrotropic agents significantly increased the solubility of ketoprofen by up to 58 times. The results indicated that the independent variables exerted a positive influence on solubility and %CDR. Furthermore, the responses were contingent on the specific hydrotropes selected, which functioned as the independent variables. Analyzing the r² and ANOVA results suggested that the dependent variables aligned well with the chosen model. Visual representations, such as the 3D response surface plot and contour plot, demonstrated the impact of each hydrotrope individually and when combined. Overall, employing hydrotropes led to improved solubility and %CDR, highlighting a direct proportionality between the rise in solubility and %CDR. Mixed hydrotropic lessens the toxicity associated with individual hydrotrope concentrations while also offering a sustainable and eco-friendly alternative. This study paves the way for future research aiming to improve the solubility of low- solubility drugs, broadening their clinical applications.

Investigation into the swelling and dissolution behaviour of Polymer-Excipient blends of PEO Utilising dissolution imaging

The use of dissolution imaging in analysing the behaviourof hydrophilic matrices and various types of excipients is examined in this study.The main aim was to investigate how different ratios of excipients with different solubility properties, such as lactose, microcrystalline cellulose, and dicalcium phosphate impact on the swelling properties and propranolol hydrochloride (PPN) release characteristics of polyethylene oxide matrix compacts. The surface properties of the compacts were investigated using a focus variation microscope after which dissolution studies were conducted to determine compact swelling and drug release properties. Smr2, a surface parameter representing the percentage of deeper valley structures on the surface, was used to calculate the proportion of the compact surface available for retaining lubrication (dissolution media in this case). Smr2 values of 83 and 84 were measured for the 1:1 and 1:3 PEO lactose compacts, respectively. This parameter utilised in this experiment gives an indication of the compact surface available for the initial hydration process and suggests a higher rate of hydration for the 1:1 and 1:3 PEO lactose compacts. The swelling studies revealed that a higher PEO ratio (3:1) resulted in more extensive gel layer formation as compared to the 1:3 compacts. All PEO:excipient compacts exhibited faster drug release than the compacts comprising PEO as the sole excipient. The quantity of PEO present was thus crucial in influencing the capacity of the matrix to control the release of PPN. This study underscores the potential for modifying drug release by altering the quantity of the matrix gel-former (PEO in this case) as well as the type or ratio of excipient used. The study also highlights the novelty of using UV dissolution imaging to image and quantify swelling and drug dissolution processes as well as providing qualitative observations such as channel formation which can support formulation optimisation and mechanistic understanding.

Meloxicam-amino acids salts/ion pair complexes with advanced solubility, dissolution, and gastric safety

Amino acids have attracted attention as a potential functional excipient for optimizing biopharmaceutics characteristics of poorly soluble drugs. The amino acids are a diverse class with many functional groups, natural compounds, biocompatible and low molecular weight substances. Two amino acids serine and arginine were investigated with meloxicam. Meloxicam has extremely low solubility; being NSAIDs, gastric upset and ulcer are common side effects. Solid dispersions were produced by precipitation and physical mixing techniques. The produced combinations underwent in vitro dissolution, docking, DSC, FTIR, XRD, solubility and gastric ulcer formation studies. Docking indicated formation of ion pair/salt between the basic amino acid arginine and meloxicam. Both solubility and dissolution rates were increased by up to 3000- and 12-fold, respectively. DSC, FTIR an XRD supported these findings. Rats treated with meloxicam showed loss of surface gastric epithelium integrity and ulceration. The animal group received meloxicam: arginine showed intact gastric mucosa with the surface epithelium and gastric glands well organized and nearly similar to the untreated control. Arginine with the guanidine group that was capable of preserving gastric mucosa after repeated administration for 10 days. This study highlighted the role of arginine as a functional excipient that did not only improve solubility and dissolution rates but ameliorated the long-standing gastric side effects attributed to meloxicam.

Phase-separated polymer blends for controlled drug delivery by tuning morphology

Controlling drug release rate and providing physical and chemical stability to the active pharmaceutical ingredient are key properties of oral solid dosage forms. Here, we demonstrate a formulation strategy using phase-separated polymer blends where the morphology provides a route for tuning the drug release profile. By utilising phase separation of a hydrophobic and a hydrophilic polymer, the hydrophilic component will act as a channelling agent, creating a porous network upon dissolution that will dictate the release characteristics. With ptychographic X-ray tomography and scanning transmission X-ray microscopy we reveal how the morphology depends on both polymer fraction and presence of drug, and how the drug is distributed over the polymer domains. Combining X-ray imaging results with dissolution studies reveal how the morphologies are correlated with the drug release and showcase how tuning the morphology of a polymer matrix in oral formulations can be utilised as a method for controlled drug release.

Dissolution of Volcanic Ash in Alkaline Environment for Cold Consolidation of Inorganic Binders.

A systematic study on the dissolution in concentrated alkali of two volcanic ashes from Cameroon, denoted as DAR and VN, is presented here. One volcanic ash, DAR, was 2 wt% richer in Fe and Ca and 4 wt% lower in Si than the other, designated as VN. Such natural raw materials are complex mixtures of aluminosilicate minerals (kaersutite, plagioclase, magnetite, diopside, thenardite, forsterite, hematite, and goethite) with a good proportion of amorphous phase (52 and 74 wt% for DAR and VN, respectively), which is more reactive than the crystalline phase in alkaline environments. Dissolution in NaOH + sodium silicate solution is the first step in the geopolymerisation process, which, after hardening at room temperature, results in solid and resistant building blocks. According to XRD, the VN finer ash powders showed a higher reactivity of Al-bearing soluble amorphous phases, releasing Al cations in NaOH, as indicated by IPC-MS. In general, dissolution in a strong alkaline environment did not seem to be affected by the NaOH concentration, provided that it was kept higher than 8 M, or by the powder size, remaining below 75 µm, while it was affected by time. However, in the time range studied, 1-120 min, the maximum element release was reached at about 100 min, when an equilibrium was reached. The hardened alkali activated materials show a good reticulation, as indicated by the low weight loss in water (10 wt%) when a hardening temperature of 25 °C was assumed. The same advantage was found for of the room-temperature consolidated specimens' mechanical performance in terms of resistance to compression (4-6 MPa). The study of the alkaline dissolution of volcanic ash is, therefore, an interesting way of predicting and optimising the reactivity of the phases of which it is composed, especially the amorphous ones.

Melt-extruded formulations of fenofibrate with various grades of hydrogenated phospholipid exhibit promising in-vitro biopharmaceutical behavior

In the current study, it was demonstrated that three commercially available grades of hydrogenated phospholipids (HPL) differing in their content of phosphatidylcholine may be used as components for hot melt-extruded binary (HPL as sole excipient) or ternary (in combination with copovidone) solid dispersions of fenofibrate (FEN) at mass fractions between 0.5 and 20% (ternary) or 80% (binary). X-ray powder diffraction indicated complete conversion of crystalline fenofibrate into the amorphous state by hot melt extrusion for all ternary blends. In contrast, both the binary blends (HPL- and copovidone-based) contained minor remaining crystallites. Irrespectively, all solid dispersions induced during dissolution studies a supersaturated state of FEN, where the ternary ASDs showed enhanced and more complete release of FEN as compared to the binary blends and, even more pronounced, in comparison to the marketed micronized and nano-milled formulations. In terms of the cumulated amount permeated, there were marginal differences between the various formulations when combined dissolution/permeation was done using FeSSIF as donor medium; with FaSSIF as donor medium, the binary HPL-ASD containing the grade with the highest phosphatidylcholine fraction performed best in terms of permeation, even significantly better than the marketed nano-crystal formulation. Otherwise, no significant differences were seen between the various grades of HPL when FEN dissolution and permeation were analyzed for ternary solid dispersions. In conclusion, the in-vitro biopharmaceutical behaviour of hydrogenated phospholipid-containing blends manufactured by hot melt extrusion appears promising. They can be a viable formulation option for poorly water-soluble and lipophilic drug compounds like FEN.

Formulation and <i>In Vitro</i> Evaluation of Aceclofenac Orally Disintegrating Tablets using the Natural Superdisintegrants

Background: Oral disintegrating tablets are engineered to dissolve in saliva extremely quickly, typically within a matter of seconds. Aim: The aim of the research was to develop and assess aceclofenac Oral Disintegrating Tablets (ODT) through wet granulation, employing natural super disintegrants in different concentrations. Methods: The chitosan was isolated from the prawn shell using different concentrations of formulated trails, including F1, F2, F3, F4, and F5. Aceclofenac orally disintegrating tablets were prepared and characterized for various parameters including hardness, friability, weight uniformity, drug content, disintegration time, and in vitro dissolution studies. Results: Among the formulations, F5 exhibited superior performance in terms of rapid disintegration with 29 sec and the highest percentage of drug release with 98.91% compared to the others. Conclusion: Increasing the concentration of isolated chitosan from prawn shell results in an increased dissolution profile and a decrease in disintegration time.

Revolutionizing fast disintegrating tablets: Harnessing a dual approach with porous starch and sublimation technique

This study investigates the transformation of neat starch (NS) from mung beans into porous starch (PS) for the formulation of fast-disintegrating tablets (FDTs) using the sublimation technique, contrasting their performance with superdisintegrants such as sodium starch glycolate (SSG) and croscarmellose sodium (CS). Camphor was used as a sublimating agent. The interaction between drug and excipients was analyzed using Fourier-transform infrared spectroscopy (FTIR), while preformulation assessments were conducted on powder blends. Model drug Diclofenac sodium (DL)-loaded FDTs were prepared via direct compression technique. Thermal behavior and crystalline properties were evaluated using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), respectively. Compressibility of tablets was assessed through Heckel and Kawakita analyses. Post-compression evaluations encompassed hardness, thickness, in vitro disintegration, and dissolution studies. FTIR analysis indicated the absence of chemical interactions among constituents, while precompression analyses confirmed favorable flow properties of the blends. Heckel analysis supported the material's notable compressibility. Microscopic examination revealed the formation of pores on the tablet surface due to the sublimation process. Integration of PS significantly accelerated the disintegration time of FDTs, with durations ranging from 50 to 82 s, compared to 76–104 s for NS-FDTs. While PS-FDTs exhibited a longer disintegration time compared to SSG, they demonstrated faster disintegration compared to croscarmellose sodium. A significant disparity (p<0.01) in drug release at 60 min was observed between SSG and PS-FDTs, with DP3 achieving 97.65 % drug release. Most batches followed the Korsmeyer-Peppas model, except for DN2 and DN3, which adhered to Higuchi-matrix drug release kinetics. Stability assessments after 90 days revealed no significant differences (p>0.05). Conclusively, this study highlights the effectiveness of PS and the sublimation method in creating FDTs with enhanced drug release properties.