FF Vaistų technologijos ir socialinės farmacijos katedra (03.06)

Background: Pelargonium sidoides DC. is a perennial plant that belongs to the Geraniaceae plant family and is primarily found in Southern Africa [1]. It‘s secondary metabolites are mostly proanthocyanidins that are linked to antioxidant, anti-inflammatory, immunomodulatory, antitumor and DNA-protective properties [2]. In this study, qualitative analysis of solid capsules containing lyophilized proanthocyanidins extracted from the dry Pelargonium sidoides DC. root extract was performed. Aim: To perform qualitative analysis of solid capsules containing lyophilized proanthocyanidins extracted from the dry Pelargonium sidoides DC. root extract. Methods: Dry Pelargonium sidoides DC. root extract was obtained from International Flavors & Fragrances Inc. (Switzerland). Proanthocyanidins were isolated and purified using Sephadex LH – 20 column chromatography with methanol (50 %) and acetone (70 %) as eluting solvents sequentially. Proanthocyanidin samples were prepared by acetone evaporation followed by lyophilization. For proanthocyanidin quantification spectrophotometric DMAC method was used with epicatechin solution as a standard. Capsule quality was evaluated by uniformity of mass and disintegration tests, as well as an in vitro release study in methanol (50 %) and hydrochloric acid medium (pH = 1.2). The statistical analysis was performed using “Microsoft Excel 2025” (Microsoft Corporation, USA). Results: The average capsule weight, determined by the uniformity of mass test, was 0.370 (0.004) g. Capsules disintegrated after 16 minutes. In methanol (50 %) medium maximum release was 8.72 mg EE/g (87.06 %) and in pH 1.2 medium maximum release was 6.22 mg EE/g (62.03 %). Conclusions: Fewer than 2 capsules out of 20 showed a mass deviation greater than 7.5 %, indicating consistent capsule filling. All capsules disintegrated in less than 30 minutes, demonstrating acceptable disintegration performance. The in vitro release study showed that release of epicatechin equivalents was dependent on the test medium: in 50 % methanol, proanthocyanidin - like compounds were released from capsules almost completely, whereas in a pH 1.2 medium the maximum release was lower, indicating limited release of epicatechin – equivalent compounds under acidic conditions.

Background: Buccal films are an innovative mucosal dosage form providing rapid onset of action, bypass of hepatic first-pass metabolism, and improved patient compliance [1]. The global market for oral polymeric films is steadily growing due to increasing demand for fast-acting antiemetic, analgesic, and neurological therapies. However, the development of a universal polymer platform with reproducible mechanical and biopharmaceutical properties, compatible with water-soluble active pharmaceutical ingredients (APIs), remains a significant challenge, particularly under small-batch manufacturing conditions. Aim: To develop and experimentally validate a universal polymer matrix for immediate-release buccal films using ondansetron hydrochloride as a model drug. Methods: A combined PVA/HPC system was formulated using polyvinyl alcohol (5.6% w/v) and hydroxypropyl cellulose (2.4% w/v) with glycerol (2% w/v) as a plasticizer. An aqueous solution of ondansetron hydrochloride (2 mg/mL, expressed as ondansetron) was incorporated into the polymer base at a 3:2 volume ratio (base:API solution) to produce 20 films. Films were prepared by solvent casting with controlled volumetric dosing (5 mL per mold) and dried at 37–38 °C for 20 h to constant weight. pH, weight uniformity, disintegration time, and dissolution were evaluated. Results: The films showed a mean weight of 0.423 g with variability below 5%, confirming reproducible dosing. The pH (5.0–5.5) corresponded to physiological oral conditions. No pronounced bitterness or irritation was observed. Rapid disintegration (1–3 min) and immediate drug release were achieved: 75% within 3 min and 100% within 5 min, consistent with immediate-release mucosal dosage forms [2]. Conclusion: The results confirm the technological reproducibility of film formation based on the developed PVA/HPC matrix, its pharmaco-technological relevance, and the feasibility of te

Background: Chamomile hydrolate is produced during the distillation process [1]. It is used to treat skin irritation, inflammation, and wound healing [2]. Steam distillation is a process in which steam is passed through the material, resulting in the collection of volatile components. Hydrodistillation is a process in which the whole material is boiled, and volatile compounds are collected [3]. Aim: To evaluate the influence of extraction apparatus on physicochemical characteristics and antioxidant activity of chamomile hydrosols. Methods: Three types of chamomile hydrolates were produced using different apparatuses and conditions. The first was collected via steam distillation for 30 minutes. The second used a Clevenger at higher temperature for one hour, and the third with a Clevenger at lower temperature. Turbidity was measured spectrophotometrically with water as a control. pH was measured with an XS pH 60 VioLab meter. Total phenolic content was determined using the Folin-Ciocalteu method (mg GA/g), and antioxidant activity with the FRAP assay (mg Fe(II)/g). Results: The highest phenol content was achieved at the highest temperature using the Clevenger method, whereas the lowest content was observed using steam distillation. The steam distillation process was also the fastest compared with the Clevenger method. The sample produced using the Clevenger apparatus had a different phenolic profile compared with the other two hydrolates when the temperature was adjusted. The first hydrolate had almost no turbidity, while the second and third were cloudy. The highest pH of 5.57 was observed in the first hydrolate, while the other two were more acidic at 4.74 and 4.70. Conclusion: The second hydrolate obtained by hydrodistillation using the Clevenger apparatus at higher temperature was deemed the most favorable due to its optimal pH for skin products and its highest phenolic content, whereas the third hydrolate, produced at a lower temperature, demonstrated the greatest antioxidant activity.

Background: Compared to traditional pharmaceutical preparations, additive manufacturing allows the development of personalised dosage forms. Direct powder extrusion (DPE) is a promising 3D printing technique that allows tablets to be manufactured directly from powder mixtures, removing the need for filament preparation. However, DPE hasn’t been widely explored in the pharmaceutical sector (1). DPE allows enteric properties to be incorporated directly into the tablet’s matrix, eliminating the need for additional coating steps (2). Aim: to develop intestine-soluble tablets through Direct Powder Extrusion using enteric polymers for 3D printing. Methods: Three formulations were prepared using different enteric polymers: PEG 4000, HPC, and Kollidon VA 64, with magnesium stearate as a lubricant. Evaluation of powders was performed in accordance with the European Pharmacopoeia 11th Edition, including flowability, bulk and tap density and moisture content. Additionally, powders were dried and granulated to evaluate the impact of extrusion performance. Tablets were printed using the M3DIMAKER pharmaceutical 3D printer, using the DPE head. Printing parameters were optimised experimentally to achieve stable extrusion. Results: Formulation 2, containing 10% PEG 4000, 30% HPC, 59% Kollidon VA 64, and 1% magnesium stearate, achieved continuous extrusion and successful printing. The tablet was successfully printed at 200 °C. Good flowability can be reflected by a compressibility index ≤5% and a Hausner index ≈1,05. In contrast, the F1 formulation exhibits poorer flow characteristics, reflected in a compressibility index of ~20%, which corresponds to unstable extrusion behaviour. F3 only extruded when in a stationary position. Drying and granulation enabled a reduction of the optimal printing temperature to 175°C. Conclusion: The experiments demonstrated that successful DPE printing not only depends on the individual polymer content but also on the polymer ratio. Additional powder preparation steps significantly improved extrusion performance and printability.

Background: Lozenges are solid dosage forms that intend to dissolve in the oral cavity or pharynx. Due to the ease of manufacturing process, pleasant taste, and versatility in delivering various drugs, soft lozenges are becoming more popular in the pharmaceutical market. The basis of soft lozenges is typically composed of binders such as polyethylene glycols, acacia or gelatin, in combination with sucrose [1,2]. Since this pharmaceutical dosage form is suitable for pediatric patients, we decided to replace sucrose with a safer alternative - polyols, due to their reduced cariogenic potential, lower effect on blood glucose levels, and improved metabolic profile [3]. Aim: The aim of this study was to assess the effect of different sweeteners on the firmness and springiness of soft lozenges. Methods: Three series of soft lozenges were prepared, differing in the type of sweetener used: xylitol in the first formulation, erythritol in the second, and a combination of xylitol and sorbitol in the third. Basis of soft lozenges contained 30% gum arabic, 30% sweetener, 25% water, 12,5% glycerol and 2,5% citric acid solution. Soft lozenges were made by casting into starch molds. Texture properties such as firmness and springiness were evaluated using a texture analyzer TA.XT.plus. Measurements were repeated three times and an average with a standard deviation was presented. Results: The firmness of the produced soft pastilles varied from 296.592±113,875 to 562,89±4.87 g while springiness varied from 16.241±0.223 to 22.81±0.76 g. Both evaluated texture parameters of the developed soft lozenges were statistically significantly higher in formulations containing xylitol and sorbitol as combination of the sweeteners. Conclusions: Based on the obtained results, polyols have a significant influence on the mechanical properties of soft pastilles. Among the evaluated formulations, the combination of xylitol and sorbitol was identified as the most suitable for the production of soft pastilles.

Background: Astaxanthin is a naturally occurring marine carotenoid which is widely found in marine organisms such as microalgae, shrimp, krill, and salmon. Because of its unique chemical structure, which includes a long conjugated polyene chain and terminal hydroxyl and keto groups, astaxanthin shows very strong antioxidant activity considerably higher than commonly used antioxidants such as vitamins C and E, and has anticancer potential, anti-inflammatory, antihypertensive, antimicrobial and neuroprotective. However, the therapeutic use of astaxanthin is limited due to its poor solubility and low bioavailability which make its effective delivery to target cells challenging. Aim(s): To develop a liposomal formulation of astaxanthin that improves its stability, bioavailability, and effectiveness at the target site. Methods: Liposomes are spherical vesicular and colloidal delivery systems which are made up of bilayer amphiphilic lipid membrane such as phospholipids and a hydrophilic core. These structures have many advantages which make drug delivery more effective. In this study, liposomal astaxanthin was prepared by using the thin-film hydration method. The formulation process was challenging. For instance, different formulation parameters such as phospholipid type, lipid ratio, organic solvent content and sonification time can significantly influence liposome formation and physicochemical characteristics. Results:The optimised formulation was analysed. In terms of particle size, a Z-average of 114 nm was observed, which confirms nanoscale liposomes suitable for drug delivery. Moreover, a Polydispersity Index (PDI) of 0.27 and a zeta potential of −19.2 mV which show uniform size distribution and colloidal stability. Also, a high encapsulation efficiency of 85% shows effective and efficient loading of astaxanthin into the lipid bilayer. To improve stability and protect astaxanthin from thermal degradation, the liposomal dispersion was converted into microcapsules by lyophilisation. Conclusion: This formulation strategy demonstrates the potential of liposomal astaxanthin microcapsules as an oral delivery system for anticancer applications.

Background: Texture is a critical quality feature of chewable gel tablets. The hardness of chewable gel tablets is affected not only by the gelling agent but also by other important ingredients like prebiotics. Prebiotics such as inulin are nondigestible carbohydrates that play important role in our intestinal health [1]. Inulin has the ability to form functional texturizing effects in gel systems by contributing to water retention and network formation [2]. Aim: To investigate the impact of the amount of prebiotics on textural parameters of chewable gel tablets. Methods: Four samples with different combination of ingredients were prepared and stored under four conditions: room temperature sealed, room temperature unsealed, refrigerated sealed, refrigerated unsealed. Hardness were obtained 3 times by texture analyser TA.XT plus. The chewable gel tablets were measured after preparation and re-measured after three months of storage. Statistical analysis was performed using Excel (Microsoft, USA). Results: Increasing inulin concentration significantly reduced hardness of chewable gel tablets (p<0.05). After three months sealed samples showed a non-significant decrease, although unsealed samples that were left in room temperature showed significantly increased hardness, especially in second and third samples (p<0.05). Refrigerated samples maintained moderate changes. Overall, inulin contributed to improved textural stability under sealed conditions. Conclusion: An increase in pectin concentration statistically significantly reduces the hardness of chewable gel tablets when stored in room temperature.

Background: Idebenone is a lipophilic antioxidant with emerging applications in mitochondrial and neurodegenerative disorders. However, its poor aqueous solubility and limited bioavailability restrict its clinical effectiveness [1]. Polymeric buccal mucoadhesive films could circumvent these limitations, which is particularly relevant for neurologic patients with dysphagia or complex polytherapy. Rational selection of excipients is critical to achieving optimal performance. In this context, in silico excipient screening tools offer a predictive and time-efficient approach to guide formulation design, reducing experimental workload while enhancing formulation success [2]. Aim(s): This study aimed to design, develop, and characterize Idebenone-loaded buccal films using in silico screening. The work focused on optimizing film composition and developing oral films to achieve appropriate mechanical strength, flexibility, swelling behavior, and mucoadhesive performance, while ensuring uniform drug incorporation. Methods: Molecular docking was used to evaluate interactions between candidate polymers and mucin-1, and to assess Idebenone-excipient compatibility. Then, oral mucoadhesive films were prepared by solvent-casting method and 3D printing. The films were characterized by critical parameters such as mechanical behavior, disintegration time, swell properties, and drug release. Results: All evaluated mucoadhesive polymers exhibited favorable interactions with mucin-1, indicating good affinity toward the mucin receptor. Among them, HPMC demonstrated the highest affinity. The highest level of compatibility was observed between Idebenone and PEG-400. Formulations with increased Gelatin and PEG-400 content demonstrated the best overall performance, particularly in terms of mechanical flexibility and mucoadhesive properties. Both fabrication methods produced films with comparable performance. Conclusion: In silico excipient screening successfully guided and optimized the development of Idebenone polymeric films by reducing experimental trials while achieving suitable characteristics for oral delivery. For neurology, optimized films may improve treatment adherence in patients.

Backround: Toothpaste tablets are eco-friendly as they lower water use and plastic waste while offering the same health benefits as traditional toothpaste [1,2]. Abrasive materials in most toothpaste remove plaque and stains with minimal damage to teeth and gums [3]. Before producing toothpaste tablets containing abrasives, it is essential that the formulation be homogeneous and have high component compatibility to ensure optimal results [4]. Aim: To develop toothpaste powder formulations with natural abrasive agents and evaluate their quality based on the effect of abrasives on tablet preparation. Methods: Three toothpaste powder formulations with varying natural abrasives were developed. The first had hydrated silica and calcium carbonate totalling 15%. The second had only hydrated silica (15%), and the third only calcium carbonate (15%). All powder components were weighed separately and mixed. Moisture content was measured using a Kern Dbs analyser. The quality of the powders was evaluated according to the European Pharmacopoeia (Ph. Eur.) methods for powder and tablet quality (2.9.5; 2.9.7; 2.9.8; 2.9.16; 2.9.34; 2.9.36). Results: The calcium carbonate formulation showed the poorest powder properties, with a Car’s index of 30.77 and Housner ratio of 1.500. The hydrated silica formulation was slightly better, with an index of 30.77 and ratio of 1.444. The mixture with both abrasives yielded the best results but still had poor flow properties, with a Car’s index of 27.27 and a Hausner ratio of 1.375. After optimization, the powder was suitable for tablet production, with tablets measuring 13.35 mm in diameter and 3.30 mm thick. When using 7.5% abrasive, tablets had unsatisfactory mechanical properties, fracturing at 110N and breaking during friability tests. Not all formulations produced acceptable tablets. Conclusion: Powders with two abrasives outperform single-abrasive ones. Use various ratios, favoring more calcium carbonate. Further improvements include adding magnesium stearate, colloidal silicon dioxide, or sieving through 0,250 – 0,150 mm to ensure homogeneity. Homogeneous powders enhance tablet quality.

Background: Tillia cordata L. is a widely used medicinal plant raw material characterised by a high content of phenolic compounds and pronounced antioxidant activity [1]. Flowers contain many phenolic compounds, and optimising extraction methods, temperature, and solvents can substantially boost the amount of active compounds [2]. One such parameter could be excipients, like αcyclodextrin. Aim: To evaluate the influence of alpha excipient on the content of phenolic compounds and antioxidant activity in extracts of Tilia cordata L. from different vendors. Methods: 0.5(0.001) g of plant material was weighed, then 10 mL of 70% ethanol solvent was added. Samples were heated in a 50 mL round-bottom flask in a sand bath with a reflux condenser at the solvent's boiling point for 1 hour. After cooling, they were centrifuged and filtered through medical gauze. For samples with α-cyclodextrin, 1% excipient was added and processed similarly. Total phenolic content and flavonoids were measured using the Folin-Ciocalteu method, expressed as gallic acid equivalents (mg GAE/g) and RE equivalents (mg RE/g). Antioxidant activity was assessed with the FRAP method, results shown as mg Fe²⁺/g. Results: In samples prepared using only reflux, T3-70R showed the highest phenolic compounds (466.2 mg GAE/g) and flavonoids (0.596 mg RE/g). However, when α-cyclodextrin was used in the extraction process, the phenolic content increased threefold, rising from 1129.77 to 1331.57 mg GAE/g. Flavonoid content ranged from 4.836 to 5.203 mg RE/g, with α-cyclodextrin increasing it significantly up to ten times. Higher phenolic content correlated with increased antioxidant activity, which rose 48% compared to the control. Post-α-cyclodextrin, antioxidant activity ranged from 10.688 to 13.833 mg Fe²⁺/g, versus 9.333 to 0.04 mg Fe²⁺/g in controls. Conclusion: α-cyclodextrin boosts phenolic compounds in extract, enhancing antioxidant activity. The use of excipients improves the extraction of phenolic-rich extracts.