Oral Dosage Forms Research Articles

Pharmacokinetics of a New Dimethylamineethanol Derivative Administered Orally to Laboratory Animals

A new derivative of dimethylaminoethanol, butanedioic and trans-butenedioic acids (laboratory code ADK-17) was synthesized at the Organic Chemistry Department of the Saint Petersburg State Chemical and Pharmaceutical University (SPSPU). This promising nootropic and anti-asthmatic agent is planned for use in an oral dosage form. The aim was to calculate the pharmacokinetic parameters of the synthesized compound and to determine its possible biotransformation pathways. Rabbits of the Soviet Chinchilla breed were used as a test system in the preclinical study of the compound pharmacokinetics. In accordance with the designed schedule, blood was taken from the marginal vein of the ear, and urine samples were taken. Quantitative determination in biological media was carried out using an Ultimate 3000 liquid chromatograph with a Q-Exactive mass-selective detector with electrospray ionization in accordance with OFS 1.2.1.100015 (Chromatography) of the State Pharmacopoeia by ultra-performance liquid chromatography–mass spectrometry (UPLC-MS). To study the pharmacokinetics of the ADK-17 preparation, a measurement procedure was developed with a detection limit in biological media ranging from 10-6 to 10-3 mg/ml. The determined harmacokinetic parameters show that the absorption of ADK-17 into the systemic circulation from the gastrointestinal tract occurs at an average rate, with its maximum concentration in blood plasma during the oral route of administration being observed between 60–90 min. The elimination half-life from the systemic circulation comprises 4.3 h. Urinary excretion in the first 4 h proceeds at a high rate; however, the compound is detected in the urine within 3 days and in the blood within 2 days from the moment of administration.

A Stable Formulation of a Non-Steroidal Anti-inflammatory Drug, Ibuprofen and an Antihistamine drug, Famotidine for a Combination Therapy

Purpose: The present research study was focused on developing an oral dosage form with two highly incompatible drugs, a non-steroidal anti-inflammatory drug, Ibuprofen and an antihistamine drug, Famotidine to be administered as a combination therapy in a single dose and further asses the stability of the finished product. Methods: A novel drug formulation was designed by employing mini tablets technology to manufacture Famotidine core tablets and the core tablets are further film coated with Opadry II coating solution to inhibit Famotidine contact with Ibuprofen matrix. Film coated Famotidine 30 mg mini-tablets were then encapsulated in Ibuprofen blend to improve the compatibility and stability of the drug product [1,2]. Each mini-tablet of Famotidine contain 5 mg dose of Famotidine and 6 such mini-tablets were encapsulated in each size “00” hard gelatin capsule containing Ibuprofen blend equivalent to 800 mg claim. The stability of the finished product was evaluated in accelerated stability conditions to ensure the impurities are well within the Pharmacopeia (USP) assigned limits. Results: The dissolution release of Ibuprofen and Famotidine is higher than 85 % in 15 minutes and is compared against the only available product in the combination therapy, DUEXIS® (Ibuprofen and Famotidine Tablets 800 mg and 26.6 mg). The stability of the final formulation is evaluated by placing the samples in 40°C/75 % RH storage condition for six months and the results of the pharmacopeia (USP) listed specified and unspecified impurities are well not more than 0.5 % w/w of the label claim. Famotidine and Ibuprofen are two highly in-compatible drugs for a combination therapy, and has been a challenge in the field to formulate for a combination therapy to improve patient compliance. The two drugs tend to form impurities at significate levels in direct physical contact during any stage of the manufacturing process.

Evolution characteristics of micromechanics provides insights into the microstructure of pharmaceutical tablets fabricated by bimodal mixtures

This research focuses on the evolution of mechanical behavior of bimodal mixtures undergoing compaction and diametrical compression. The clusters were built and discrete element method (DEM) was used to investigate the densification process and micromechanics of bimodal mixtures. Additionally, a more comprehensive investigate of the respective breakage of the bimodal mixtures has been carried out. On this basis, qualitative and quantitative analysis of the compressive force, force chain, contact bonds and density field evolution characteristics of the clusters are investigated during the compression process. The entire loading process of the clusters is divided into three stages: rearrangement, breakage and elastic–plastic deformation. Additionally, there are differences in the evolution of micromechanics behavior of different particles in the bimodal mixture, with pregelatinized starch breakage and deformation occurring before microcrystalline cellulose. With the tablet deformation, the fragmentation process of the tablet started at the point of contact and extended toward the center, and the curvature of the force chain increased. This approach may potentially hold a valuable new information relevant to important transformation forms batch manufacturing to advanced manufacturing for the oral solid dosage form.

A comprehensive compatibility study of ganciclovir with some common excipients

Objectives: The aim of the present study is to illustrate compatibility testing of ganciclovir (GCV) with some common excipients that would be used to manufacture solid oral dosage forms. Different spectroscopy techniques were utilized to see the interaction of GCV with excipients such as lactose, microcrystalline cellulose (MCC), magnesium stearate, and talc, and dicalcium phosphate. Further, a molecular docking study was also done to know the interaction of GCV with excipients. In vitro study of a physical mixture of GCV with excipients was performed to get the release of drug. Material and Methods: A number of analytical techniques (differential scanning calorimetry [DSC] using DSC-Q20, TA instruments, Fourier-transform infrared spectroscopy [FTIR] spectroscopy using Spectrum RX 1, nuclear magnetic resonance [NMR] using Bruker Advance Neo 500 MHz NMR spectrometer, etc.) have been used to explore the drug-excipient compatibility. Further, a suspected interaction was evaluated by thin-layer chromatography (TLC). In vitro dissolution studies in different sets of experiments were accomplished to determine the influence of hydrophobic and hydrophilic attributes of excipients (MCC, lactose, dicalcium phosphate, and talc) on the dissolution profile of GCV using USP1-type dissolution apparatus. Furthermore, in silico molecular docking studies were also performed to evaluate any probable molecular interactions among drugs and excipients using Auto Dock VINA 1.2.0 software and GROMACS 5.0 software. Results: Comparing FTIR and 1H NMR spectra of GCV and physical mixtures of GCV and excipients, no significant deviation of characteristic peaks in infrared spectroscopy and 1H NMR signals was observed. The DSC of GCV showed two sharp endothermic peaks at 238.82°C and 255°C. The endothermic peak of GCV in DSC thermogram of physical mixtures was observed in nearly the same position except with lactose and dicalcium phosphate. A slightly deviated peak of GCV with a physical mixture of drug and lactose and dicalcium phosphate indicated that there were suspected interactions between the drug with lactose and dicalcium phosphate. These interactions were evaluated by thin-layer chromatography (TLC) and it confirmed that there was no interaction between drugs and excipients. In vitro dissolution studies determined the influence of hydrophobic and hydrophilic attributes of excipients on the dissolution profile of GCV. The physical mixture of GCV with MCC displayed a maximum amount (66.48%) of drug release in 10 min. On the other hand, a physical mixture of GCV with talc showed a minimum amount (12.08%) of drug release in 10 min. Docking study predicted that the number of interactions were more between GCV and lactose (four nos.) in comparison to GCV and MCC (two nos.). This interaction supported the in vitro drug release of a physical mixture of GCV with MCC which was higher than a mixture of GCV with lactose. Conclusion: Compatibility testing of GCV with used excipients by analytical techniques confirmed that GCV should be compatible with used excipients. Drug dissolution of GCV and physical mixture of MCC exhibited the maximum amount of drug release whereas a mixture of GCV with talc released the minimum amount of drug for both short (10 min.) and long (60 min.) periods. Docking studies disclosed that the lactose complex showed less deviation with less root mean square deviation value in comparison to the microcrystalline complex. Thus, the lactose complex has more hydrogen bonds and it was more stable as compared with the MCC complex. GCV indicates that the total energy of the MCC complex is less than that of the lactose complex. This indicates that GCV is more soluble when combined with the microcrystalline complex. Therefore, GCV and used excipients could be used for solid dosage formulations.

In Vitro and In Vivo Evaluation of Dark Chocolate as Age-appropriate Oral Matrix

Swallowing difficulties encountered by geriatric patients who undergo polypharmacy represent a significant challenge that hampers patient compliance and therapeutic management. As an appealing and sensory-pleasing, chocolate-based formulations have emerged as a potential alternative oral dosage form suitable for both the elderly and paediatric populations. However, the extent to which the incorporation of drugs into a chocolate matrix affects their oral availability remains unclear. Therefore, the objective of this investigation was to explore the in vitro and in vivo performance of an ibuprofen-based chocolate dosage form. A matrix based on dark chocolate and the model drug was prepared at two distinct temperatures: 50 and 80 °C. In vitro release studies revealed that ibuprofen formulated through co-melting at 80 °C exhibited a statistically significant slower drug release (p < 0.05) compared to formulations prepared at 50 °C in both FaSSGF (fasted-state simulated gastric fluid) and lipolysis media. The enzymatic degradation of chocolate in the presence of lipase accelerated in vitro ibuprofen release from chocolate matrices. To delve deeper into the bioavailability of ibuprofen within the chocolate formulations, we conducted an in vivo assessment, comparing the pharmacokinetic profiles of ibuprofen in its conventional suspension form with our chocolate-based dosage forms. A notable drop (p < 0.05) in the maximum serum concentration of ibuprofen when incorporated into co-melted or solid-suspension chocolate matrices. However, no significant differences in plasma exposure were observed between the two formulations. These findings shed a light on the potential of chocolate to extend of ibuprofen when integrated into various chocolate matrices, showcasing the potential held by these innovative formulations.

Untapped options to reduce waste from blister packaging for tablets and capsules

PurposeIn Europe, most medicines are taken orally and primarily packaged as single solid oral dosage forms (SODF) in blister chambers (alveoli) arranged on blister cards. Blister cards are constructed as multilayer laminates of aluminum (Al) foils and/or various plastic polymers bonded together, forming the alveoli, which are separated by more or less large gaps. We calculated the amount of packaging material (and thus waste) generated annually for the packaging of the most commonly prescribed SODF in Germany and estimated how much waste could be saved by rearranging the alveoli.MethodsFor this purpose, we analysed the SODF of the 50 most frequently prescribed medicines that were packaged in alveoli (N = 45; 13 of aluminum-aluminum blisters, 32 of mixed materials), measured and weighed their packaging material and content, calculated the annual amount of waste produced from them, and estimated how much waste could be saved if the alveoli were optimally positioned on the blister cards. In addition, we examined the variability of the blister packaging of eight groups of commonly prescribed generics of the same strength.ResultsDetailed analysis of the blister cards revealed that most of the material (69%) was used for the space between blisters and that aluminum-aluminum alveoli were more than four times larger than the packaged SODF. The (conservatively) estimated annual amount of composite waste generated for the primary packaging of these SODF was 3868 t (and extrapolated to the entire German pharmaceutical market 8533 t), of which an optimized arrangement of the blister chambers, i.e., a 2-mm sealing area around each alveolus and the arrangement of the SODF in 2 rows, would save approximately 37%.ConclusionConsidering that other ecological strategies are not yet mature, the optimal arrangement of blister chambers would be a captivatingly simple and, above all, immediately implementable strategy to avoid large amounts of avoidable waste.

Orally Disintegrating Film: A Review of Its Formulation and Manufacturing Method

Oral route drug delivery system is still considered as the most convenient and patient friendly drug delivery route. Over the decades, many research has been performed to improve the functionality oral dosage form. Orally disintegrating film (ODF) is a newer oral drug delivery system, which is in the form of a thin film that will disintegrate in the oral cavity within a matter of seconds. The aim of this review paper is to recap ODF, its benefits, formulation contents and manufacturing method. With more research and development work has been conducted on ODF, the dosage form is expected to be manufactured and scaled up to be commercializable products to be sold in the market.

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Isavuconazonium Sulfate

A Biopharmaceutics Classification System (BCS)-based biowaiver monograph is presented for isavuconazonium sulfate. A BCS-based biowaiver is a regulatory option to substitute appropriate in vitro data for in vivo bioequivalence studies. Isavuconazonium sulfate is the prodrug of isavuconazole, a broad-spectrum azole antifungal indicated for invasive fungal infections. While the prodrug can be classified as a BCS Class III drug with high solubility but low permeability, the parent drug can be classified as a BCS Class II drug with low solubility but high permeability. Interestingly, the in vivo behavior of both is additive and leads isavuconazonium sulfate to act like a BCS class I drug substance after oral administration. In this work, experimental solubility and dissolution data were evaluated and compared with available literature data to investigate whether it is feasible to approve immediate release solid oral dosage forms containing isavuconazonium sulfate according to official guidance from the FDA, EMA and/or ICH. The risks associated with waiving a prodrug according to the BCS-based biowaiver guidelines are reviewed and discussed, noting that current regulations are quite restrictive on this point. Further, results show high solubility but instability of isavuconazonium sulfate in aqueous media. Although experiments on the dissolution of the capsule contents confirmed ‘very rapid’ dissolution of the active pharmaceutical ingredient (API) isavuconazonium sulfate, its release from the commercial marketed capsule formulation Cresemba is limited by the choice of capsule shell material, providing an additional impediment to approval of generic versions via the BCS-Biowaiver approach.

Films as innovative oral dosage forms (review)

The development of new methods of delivery of biologically active substances is a promising direction. This article discusses the fields of films application, the existing classification, as well as the advantages of the dosage form.

Optimization of solid oral dosage form administration to patients with swallowing difficulties: An integrative review.

To appraise and synthesize research investigating optimizing the administration of solid oral dosage forms (SODFs) to adults with swallowing difficulties. An integrative review. An electronic search was conducted on Medical Literature Analysis and Retrieval System Online (Public Medline interface), Elsevier SciVerse Scopus and Scientific Electronic Library Online (updated February 2023). Restriction regarding the publication date was not considered for the inclusion of records. Studies addressing risks, general aspects, recommendations about patient postural adjustments, swallowing techniques, swallowing aids and aspects of concealment of SODFs were included. Fifty-three records published between 2002 and 2021 were included. The main administration risks were aspiration, asphyxia and solid oral dosage form-induced oral/oesophageal mucosal lesions. The most frequent general aspect reported was administering one oral dosage form at a time. The sitting position was the most patient postural adjustment mentioned. The most frequently reported solid oral dosage form swallowing technique was the lean-forward method for capsules. Solid oral dosage form swallowing aids cited: tongue and throat lubricant and solid oral dosage form coating device, swallowing cup and swallowing straw. The literature data on administering SODFs for adults with swallowing difficulties were appraised and synthesized. Some aspects, for example, not administering SODFs simultaneously, can make swallowing safer. Postural adjustments and solid oral dosage form swallowing aids are important to avoid administration risks. Swallowing SODFs can be easier if learned by techniques. Liquid and food are helpful as vehicles, and several of these have been listed. By optimizing the contributing factors of administering oral pharmacotherapy, the nurse can use appropriate practices to improve patient safety. Additionally, knowing and establishing the administration aspects are reasonable steps for standardizing care for patients with swallowing oral dosage form difficulties. This study addressed administering SODFs to adult patients with swallowing difficulties. The administration of SODFs to adult patients with swallowing difficulties can be optimized if only one oral dosage form at a time is administrated and if patient postural adjustments, swallowing techniques and swallowing aids are used. This investigation will impact the care of patients with swallowing difficulties. The authors declare they adhered to the relevant EQUATOR guidelines and report following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. No patient or public contribution.

Characterization and Reverse Engineering of Pharmaceuticals: Role of Thermoanalytical Techniques

During pharmaceutical or biopharmaceutical drug product development, one of the most important steps to be followed is characterization and reverse engineering of the drug product. Out of so many characterization tools and orthogonal reverse engineering techniques, thermoanalytical methods are the most useful techniques. Different thermoanalytical techniques are used to identify, quantify and understand the interaction between different polymorphic forms of drug substances and excipients. These techniques are also used to monitor the physical form (amorphous or crystalline) of the drug substance in drug product throughout its manufacturing processes and helps in identifying, omitting or modifying the steps or processes responsible for change in physical or polymorphic form of the drug substance in the finished drug product. Thermoanalytical techniques are not only useful for characterization of small molecules but also extensively applied in analysis of biological samples and nano-formulations. In current scenario, pharmaceutical development specifically during generic drug development the most useful step is the reverse engineering. When reverse engineering of drug product is concerned, thermoanalytical techniques are the best tools to be used to prove the similarity of physico-chemical properties or same state of matter or arrangement of matter between test and reference products. However, in earlier days these techniques were not used as frequently as the other techniques like spectroscopy and chromatography. Various reasons for limited use of thermoanalytical techniques were unavailability of software or compatible hardware, manual sampling process and a tedious process of manual calculation which consumes lots of time. Now a day, due to advancement of technology, automation, use of robotics, and better understanding, and the thermal analysis not only become a powerful tool but also increase the throughput. The present review focuses on some of the most commonly used Thermoanalytical techniques e.g. Differential Scanning Calorimeter (DSC), Thermogravimetric Analysis (TGA), Solution Calorimeter (SC), Thermo Mechanical Analysis (TMA) and Isothermal Titration Calorimeter (ITC) for characterization and reverse engineering of different dosage forms like solid oral dosage forms, injectable formulation, inhalation formulation, ophthalmic formulation, and biosimilar formulation products such as peptides and proteins using specific case studies.

Development of an Administration Guideline of Oral Medicines to Patients with Dysphagia.

Background and Objectives: There is increasing evidence that patients with dysphagia often have limited access to suitable oral dosage forms, especially when administered via an enteral feeding tube (FT). In addition, there is a lack of clear and readily available information from drug manufacturers on how to administer medications to patients with dysphagia. This study aimed to develop a practical guide for healthcare professionals to increase the safe and effective administration of oral medications to patients with dysphagia. Materials and Methods: The data were collected from existing English databases and handbooks available to develop an easy-to-use tabular guideline presenting all relevant information using keywords and short expressions. The working group differentiated 514 formulation types, and the information was collected and added to the guideline separately. In addition, the instructions for the patients taking the medicines orally or via FT were described separately. Results: The guideline consisted of 24 keywords or short expressions developed by the working group and described the instructions to use them. The guideline contained 343 active pharmaceutical ingredients and 19 fixed-dose combinations. Conclusions: Knowledge about proper medication preparation and administration for patients with swallowing difficulties is limited but essential. It is crucial to encourage drug manufacturers to provide this information as a standard to ensure the safe and effective use of medications for all patient groups.

Chemical Composition and Insulin-Resistance Activity of Arginine-Loaded American Cranberry (Vaccinium macrocarpon Aiton, Ericaceae) Leaf Extracts.

One of the key pathogenetic links in type 2 diabetes mellitus (T2DM) is the formation of insulin resistance (IR). Besides a wide selection of synthetic antidiabetic drugs, various plant-origin extracts are also available to support the treatment of T2DM. This study aimed to investigate and gain knowledge of the chemical composition and potential IR correction effect of American cranberry (Vaccinium macrocarpon Aiton) leaf extracts and formulate novel 3D-printed oral dosage forms for such extracts. The bioactivity and IR of L-arginine-loaded cranberry leaf extracts were studied in vivo in rats. The cranberry leaf extracts consisted of quinic, 3-caffeoylquinic (chlorogenic), p-coumaroylquinic acids, quercetin 3-O-galactoside, quercetin-3-O-glucoside, quercetin-3-xyloside, quercetin-3-O-arabino pyranoside, quercetin-3-O-arabinofuranoside, quercetin 3-O-rhamnoside, and quercetin-O-p-coumaroyl hexoside-2 identified by HPLC. In vivo studies with rats showed that the oral administration of the cranberry leaf extracts had a positive effect on insulin sensitivity coefficients under the insulin tolerance test and affected homeostasis model assessment IR levels and liver lipid content with experimental IR. A novel 3D-printed immediate-release dosage form was developed for the oral administration of cranberry leaf extracts using polyethylene oxide as a carrier gel in semi-solid extrusion 3D printing. In conclusion, American cranberry leaf extracts loaded with L-arginine could find uses in preventing health issues associated with IR.

Structured solubility behaviour in fed simulated intestinal fluids

Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in vitro is limited and multiple simulated intestinal fluid recipes have been developed but with no consensus which is optimal. This study has utilised nine bioequivalent simulated fed intestinal media recipes that cover over 90% of the compositional variability of sampled fed human intestinal fluid. The solubility of 24 drugs (Acidic; furosemide, ibuprofen, indomethacin, mefenamic acid, naproxen, phenytoin, piroxicam, valsartan, zafirlukast: Basic; aprepitant, atazanavir, bromocriptine, carvedilol, dipyridamole, posaconazole, tadalafil: Neutral; acyclovir, carbamazepine, felodipine, fenofibrate, griseofulvin, itraconazole, paracetamol, probucol) has been assessed to determine if structured solubility behaviour is present. The measured solubility behaviour can be split into four categories and is consistent with drug physicochemical properties and previous solubility studies. For acidic drugs (category 1) solubility is controlled by media pH and the lowest and highest pH media identify the lowest and highest solubility in 90% of cases. For weakly acidic, basic and neutral drugs (category 2) solubility is controlled by media pH and total amphiphile concentration (TAC), a consistent solubility pattern is evident with variation related to individual drug media component interactions. The lowest and highest pH × TAC media identify the lowest and highest solubility in 70% and 90% of cases respectively. Four drugs, which are non-ionised in the media systems (category 3), have been identified with a very narrow solubility range, indicating minimal impact of the simulated media on solubility. Three drugs exhibit solubility behaviour that is not consistent with the remainder (category 4). The results indicate that the use of two bioequivalent fed intestinal media from the original nine will identify in vitro the maximum and minimum solubility values for the majority of drugs and due to the media derivation this is probably applicable in vivo. When combined with a previous fasted study, this introduces interesting possibilities to measure a solubility range in vitro that can provide Quality by Design based decisions to rationalise drug and formulation development. Overall this indicates that the multi-dimensional media system is worthy of further investigation as in vitro tool to assess fed intestinal solubility.

Adult Patients with Difficulty Swallowing Oral Dosage Forms: A Systematic Review of the Quantitative Literature.

The aim of this systematic review was to identify and critically appraise the available evidence regarding solid oral dosage forms (SODFs), e.g., tablets, and challenges regarding the oral administration of medicine to inpatients in a variety of healthcare settings such as (1) hospitals, (2) nursing homes and (3) long-term stay units (LTSUs). A literature search was undertaken in September 2021 and repeated in June 2023 in the following databases: PubMed, EMBASE, CINAHL, Scopus, Web of Science, The Cochrane Library, PsycINFO and ProQuest. A Microsoft Excel® spreadsheet was devised to collate the following data from each eligible study: study author and year, country, number of participants, title, duration (follow-up period), study design, inclusion and exclusion criteria, method and data collection, relevant outcomes, and key findings. A total of 3023 records were identified, with 12 articles being included in the final systematic review. Seven of the twelve studies reported on the prevalence of difficulties swallowing SODFs, which varied from 10-34.2%. Nine of the twelve studies reported the methods used to manipulate SODFs, with the most reported method being tablet crushing. Given the prevalence of swallowing difficulties and the subsequent crushing of medicines in response to this, it is evident that concerns should be raised regarding the potential for a medication administration error to occur.

Flurbiprofen cataplasms: Development and validation of in-vitro dissolution methods and evaluation of multimedia dissolution profiles

The investigation of the systemic release performance of dosage forms using in vitro tools is a crucial objective in the realm of pharmaceutical development. The dissolution methodology is an effective tool for monitoring batch-to-batch variabilities in quality control and gaining insight into the release mechanisms of pharmaceutical drugs. The majority of the dissolution techniques that have been approved are primarily intended for solid oral dosage forms. Nevertheless, these techniques have also been applied to various other dosage forms, including transdermal drug delivery systems. The administration of medication through cataplasm, a transdermal application, poses challenges in understanding the characteristics of drug release. Flurbiprofen is classified as a class II drug according to the Biopharmaceutics Classification System and is commonly administered in the form of a cataplasm for its analgesic properties. A dissolution method was developed to assess the in vitro release profile of the flurbiprofen transdermal delivery system. This method utilized a United States Pharmacopeia dissolution apparatus V, with a disc assembled over the paddle. Additionally, a method for quantification was developed using liquid chromatography. The discriminatory aspect of the developed method has faced criticism due to substantial alterations in excipient composition. Furthermore, we have developed clearly defined multimedia release profiles within the physiological pH range. The validation of the dissolution and chromatography systems was conducted.

Selective laser sintering additive manufacturing of solid oral dosage form: Effect of laser power and hatch spacing on the physico-technical behaviour of sintered printlets

Selective laser sintering is a laser-based powder bed fusion 3D printing technique in which, the laser parameters plays a vital role in the fusion of polymeric powder particles and the behavior of the final printed object. Hence, the objective of the current study was to investigate the impact of laser power and hatch spacing on the fusion of particles, followed by their physicochemical and mechanical behavior investigations of the final sintered object made with dapsone and poly (1-vinylpyrrolidone-co-vinyl acetate) as a model drug and polymer, respectively. An increase in laser power and a decrease in hatch spacing improved particle fusion, resulting in smoother surface, increased density, and better mechanical properties. Interestingly, there was a loss of drug crystallinity was experienced in respect to varied laser parameters, highlighting the potential of laser-based powder bed fusion technique in developing amorphous solid dispersions. Despite extensive laser parameters, drug entrapment efficiency was found to be greater than 90 % for all sintered batches. No notable differences were observed in the dissolution behavior of all performed samples although it was anticipated to achieve as there was differences witnessed in porosity and disintegration time. Finally, the oral pharmacokinetics study revealed the comparable performance of the sintered dosage form with the tablet prepared with conventional direct compression techniques. Overall, these findings demonstrate that with varying laser parameters, various properties of the final sintered object can be manipulated which further showed the flexibility of this 3D printing technique to fabricate dosage form with a more personalized and customized needs.

Development of a Multifunctional Oral Dosage Form via Integration of Solid Dispersion Technology with a Black Seed Oil-Based Self-Nanoemulsifying Drug Delivery System.

Lansoprazole (LZP) is used to treat acid-related gastrointestinal disorders; however, its low aqueous solubility limits its oral absorption. Black seed oil (BSO) has gastroprotective effects, making it a promising addition to gastric treatment regimens. The present study aims to develop a stable multifunctional formulation integrating solid dispersion (SD) technology with a bioactive self-nanoemulsifying drug delivery system (SNEDDS) based on BSO to synergistically enhance LZP delivery and therapeutic effects. The LZP-loaded SNEDDS was prepared using BSO, Transcutol P, and Kolliphor EL. SDs were produced by microwave irradiation and lyophilization using different polymers. The formulations were characterized by particle apparent hydrodynamic radius analysis, zeta potential, SEM, DSC, PXRD, and in vitro dissolution testing. Their chemical and physical stability under accelerated conditions was also examined. Physicochemical characterization revealed that the dispersed systems were in the nanosize range (<500 nm). DSC and PXRD studies revealed that lyophilization more potently disrupted LZP crystallinity versus microwave heating. The SNEDDS effectively solubilized LZP but degraded completely within 1 day. Lyophilized SDs with Pluronic F-127 demonstrated the highest LZP dissolution efficiency (3.5-fold vs. drug) and maintained chemical stability (>97%) for 1 month. SDs combined with the SNEDDS had variable effects suggesting that the synergistic benefits were dependent on the formulation and preparation method. Lyophilized LZP-Pluronic F127 SD enabled effective and stable LZP delivery alongside the bioactive effects of the BSO-based SNEDDS. This multifunctional system is a promising candidate with the potential for optimized gastrointestinal delivery of LZP and bioactive components.

Nanoparticles loaded with natural medicines for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that disrupts cognitive function and severely affects the quality of life. Existing drugs only improve cognitive function and provide temporary relief of symptoms but do not stop or delay disease progression. Recently, natural medicines, especially Chinese herbal medicines, have gained attention in the treatment of AD due to their antioxidant, anti-inflammatory, and neuroprotective effects. However, conventional oral dosage forms lack brain specificity and have side effects that lead to poor patient compliance. Utilizing nanomedicine is a promising approach to improve brain specificity, bioavailability, and patient compliance. This review evaluates recent advances in the treatment of AD with nanoparticles containing various natural medicines. This review highlights that nanoparticles containing natural medicines are a promising strategy for the treatment of AD. It is believed that this technology can be translated into the clinic, thereby providing opportunities for AD patients to participate in social activities.

Development of olanzapine solid dispersion by spray drying technique using screening design for solubility enhancement.

Olanzapine (OLZ) is a psychotropic class drug commonly used to treat schizophrenia, bipolar disorder, and acute manic episodes. It has less water solubility, resulting in a slow dissolution rate and oral bioavailability. Therefore, the development in oral dosage forms is required to enhance the drug solubility. The solid dispersion of olanzapine is prepared by spray drying technique. The solution of polyvinylpyrrolidone K-30 (PVP K-30), mono amino glycyrrhizinate pentahydrate (GLY), OLZ and silicon dioxide were dissolved in distilled water and ethanol and spray dried to get the solid dispersion. Solid dispersion was characterized for surface morphology, solubility, encapsulation efficiency (EE), X-ray diffraction (X-RD), Differential Scanning Calorimeter (DSC) and drug-polymer interaction by Fourier transforms infrared spectroscopy. The amorphous nature of the drug's incorporation in solid dispersion was confirmed by X-RD analysis. Prepared solid dispersion showed higher solubility, 11.51 mg, than pure OLZ (0.983 mg ml-1), while the range of EE was found to be between 64 to 90 %. The solubility and dissolution rate of the OLZ can effectively increase by spray-dried solid dispersion. Plackett-Burman screening design plays a vital role in understanding the effect of independent variables on EE and solubility.