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Summary Objectives The main aim of the study was to develop an economical, insightful, accurate and simple RP-HPLC-DAD method with high precision and good sensitivity for concurrent determination of Tenofovir disoproxil fumarate, Doravirine and Lamivudine in blended bulk form and their combined tablet form. Material and methods A method with Ascentis C18 (150 × 4.6 mm, 5 μm) column, mobile phase ratio of 0.1% ortho phosphoric acid and Acetonitrile in 70:30 (v/v), 1 mL/min flow rate and detection wavelength of 260 nm was highly proficient in effective separation of all three drugs. The developed method was validated in accordance with ICH specifications. Results The retention times of Doravirine, Lamivudine and Tenofovir disoproxil fumarate observed were 2.4, 2.9, and 3.6 min, respectively. The linear responses were observed for Doravirine, Lamivudine and Tenofovir disoproxil fumarate in the range of 12.5–75 μg/mL, 75–225 μg/mL and 75–225 μg/mL, respectively. The limit of detection and quantification values were calculated to be 0.36 μg/mL and 0.11 μg/mL for Lamivudine, 0.55 μg/mL and 1.66 μg/mL for Tenofovir disoproxil fumarate and 0.03 μg/mL and 0.09 μg/mL for Doravirine. The % RSD values of the intra-day and inter-day precision were calculated in the range of 0.134–1.749. The mean percentage recovery of all three analytes was in the range of 98.85–100.18%. The statistical results of the validation parameters ensured that the method was accurate, specific, and precise with good sensitivity. Investigation of analytes under different stressed conditions ensures the stability of analytes reflecting the stability indication of the method. The developed method has high proficiency in separation of Tenofovir disoproxil fumarate, Doravirine and Lamivudine. The degradation products generated due to stress conditions also separated with good resolution. Conclusion The current method is a stability-indicating assay method consisting of appropriate specificity, accuracy, precision and sensitivity. The developed method has a good potential to be adopted by the pharmaceutical industrial sector.

Проведена валидация технологического процесса препарата «Глюконил®, таблетки, покрытые оболочкой, 1000 мг». Для каждой критической стадии процесса определены оптимальные параметры технологического процесса, установлен перечень контролируемых показателей качества, влияющих на безопасность и эффективность лекарственного препарата, и критерии их приемлемости, разработана рациональная схема отбора образцов, обеспечивающая их репрезентативность. Результаты, полученные при производстве трех промышленных валидационных серий, доказывают постоянство и надежность процесса производства лекарственного препарата от серии к серии и для каждой единицы дозированной лекарственной формы. The technological process of the preparation «Gluconil®, coated tablets, 1000 mg» was validated. For each critical stage of the process, the optimal parameters of the technological process are determined, a list of controlled quality indicators affecting the safety and efficacy of the medicinal product, and the criteria for their acceptability are established, a rational scheme for sampling is developed, ensuring their representativeness. The results obtained in the production of three industrial validation batches prove the consistency and reliability of the production process of the medicinal product from batch to batch and for each unit of the dosage form.

Pulsatile drug delivery system is one type of drug delivery system, where the delivery device is capable of releasing drugs after a predetermined time-delay (i.e. lag time). This system has a peculiar mechanism of delivering the drug rapidly and completely after a "lag time," i.e., a period of "no drug release." These systems are beneficial for drugs having high first-pass effect drugs administered for diseases that follow chrono pharmacological behavior such as drugs having specific absorption sites in GIT, targeting to colon; and cases where nighttime dosing is required. The objective of the present study was to formulate and evaluate a press coated pulsatile drug delivery system of simvastatin in order to attain a time controlled release to lower the blood cholesterol level by releasing the drug with a distinct predetermined lag time of five hrs. Simvastatin is a water insoluble drug and its absorption is dissolution rate limited. The core formulations were composed of simvastatin and disintegrants like lycoat, SSG, ludiflash in different ratios and was coated with xanthan gum, guar gum, HPMC K4M, HPMC K15M as a release modifier. Press coated tablets were evaluated for hardness, friability, drug content, and in vitro drug release. Result of in vitro dissolution study of the prepared tablet suggested that, the release of drug from press coated tablets match with chrono-biological requirement of disease.

White pomegranate peel has many kinds uses, one of them as antimalaria. The unpleasant appearance and bitter taste of white pomegranate peel tablet can be covered by film coated using Kollicoat Protect. This research aimed to determine the effect of concentration and type of solvent used as a coating on the physical properties of the coated tablets and determine the optimum formula. Tablets were made using direct compression method and then coated using Kollicoat Protect. The optimization of coating formula was performed using a factorial design with design expert software ver 10.0. Responses used were tablet hardness, friability, disintegration time and increasing tablet mass. The results of this study showed that Kollicoat Protect cause increase of weight gain tablets and decrease the tablet friability, but prolong the disintegration time of tablets and decrease the tablet hardness while type of solvent can increase of weight gain tablets, tablet hardness, and decrease the tablet friability but prolong the disintegration time of tablets. The optimum combination formula was Kollicoat Protect at 13.6% and combination of water:alcohol (1:0.863) (w/v) with a theoretical response to weight gain of 2.340%; hardness 7.950 kp; friability 0.022%; and disintegration time 20.938 minutes.

Modern research has shown that cognitive impairments are directly related to behavioral disorders and psychopathological syndromes. Nootropic drugs used for pharmacotherapy of cognitive impairments demonstrate low clinical efficiency for the treatment of psychoemotional disorders. In this case, it is advisable to correct such states by prescribing sedatives that have an integrated effect on etiological factors, pathogenetic links and symptomatic manifestations of the disease. The aim of the research was to carry out a comprehensive assortment analysis of sedative drugs within the pharmaceutical market of Ukraine. Materials and methods. Studies were carried out through generally accepted statistical and marketing studies (State Register of Medicines of Ukraine, September, 2020). Our research focused on the information on the structure of the market of sedatives registered in Ukraine. Graphical and logical methods were used in the course of the study. Results. The results of the study have shown that the products manufactured in the Ukrainian pharmaceutical enterprises take 71.50 % of this segment; whereas sedatives produced in Germany – 7.50 %; in Poland – 3.56 %; in Italy, Slovenia, France – 1.50 % for each respectively; in Austria, Malta, Great Britain – 1.02 % for each respectively. The preparations of this group are represented in solid (tablets, coated tablets, capsules, granules, herbs in packs and filter bags) and liquid (tinctures, drops, liquid extracts, elixirs, syrups, oral solutions) dosage forms. Among the studied medicines, solid dosage forms predominate; their share makes 62.7 % of the assortment, and the highest percentage rate is held by tablets (45.5 %). The largest market share of liquid medicinal forms is made by tinctures, in particular 18.9 %. The lowest percentage rates are observed in such medicinal forms as liquid extracts, drops, elixirs, syrups and oral solutions (15.5 % in general). Analysis of the state of the Ukrainian pharmaceutical market of sedatives shows that synthetic drugs account for 24.55 % of the market (tablets – 92.7 %), natural (plant) medicines – 75.45 % (solid dosage forms – 89.6 %). Conclusions. Marketing studies were carried out on the modern market of sedative medicines in Ukraine. It has been established that the quantitative and qualitative diversity of the current assortment is presented by the imported drugs and domestic producers. Analysis of the state of the Ukrainian pharmaceutical market of sedatives was performed. Sedative preparations of natural (plant) origin have been found to be predominant and occupy 2/3 of the total range of sedatives registered in Ukraine as of September, 2020. Synthetic sedative drugs are mainly combined. Monodrugs of plant origin make up the majority of assorted items. Development of drugs aimed at providing complex pharmacotherapeutical correction of cognitive and psychoemotional disorders and based on such peptides as vasopressin, is one of the most significant and relevant problems in modern neurology and is of great scientific and practical value.

The objective of this study was to understand the impact of coating excipients on the chemical stability of active pan coated peliglitazar, which was prone to acid as well as base-catalyzed degradation. Four different coating formulations containing either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC) as a coating polymer and triacetin (glycerol triacetate) or polyethylene glycol (PEG) as a plasticizer/detackifier were used for coating of peliglitazar in a perforated pan coater. Tablets of one-milligram strength were manufactured by suspending the drug in the coating suspension and spray coating onto inert core tablets. The active coated tablets were placed on stability (40 °C/75% RH) in high-density polyethylene (HDPE) bottles in closed condition with desiccants or in open condition. Tablet samples were withdrawn and analyzed for degradants using a stability-indicating HPLC method. The overall stability for the film-forming polymer-plasticizer/detackifier combination showed the rank order: HPMC-triacetin PVA-triacetin HPMC-PEG PVA-PEG. Higher stability of triacetin systems over PEG systems was attributed to lower solubility of peliglitazar in triacetin coating systems. For the same plasticizer/detackifier, higher stability of HPMC over PVA-based formulations was attributed to lower solubility and mobility of peliglitazar in HPMC compared with the PVA-based coating.

Metformin hydrochloride is a biguanide class of drug widely used to treat Type 2 diabetes mellitus. Its oral bioavailability is about 50 to 60 % with a half-life of about 3 h. This study focused on evaluation and comparison of the physicochemical properties of different brands of metformin hydrochloride (500mg) film coated tablets available in drug retail outlets in Addis Ababa, Ethiopia. Some different in vitro tests including hardness, weight variation, disintegration time, dissolution study, and assay were conducted as per United States Pharmacopeia. To compare dissolution profiles of the generic products against the innovator product (product A), a model independent method, similarity factor (f2), was also used. Weight variation result showed that all brand fall within the 5% limit from the average which is acceptable. Disintegration time of less than 15 minutes was observed for all brands. The in vitro drug release study results for the products ranged between 82 and 93% release within 30 minutes which is above 80% limit as per the United States Pharmacopeia requirement. The similarity f2 values for generic products ranged from 53 to 75%. Furthermore, assay value of the studied brands varied from 95.60 to 104.37% which was within standard limit (95-105%). It can be concluded that all brands of metformin hydrochloride tablets met pharmacopoeial specification for the tested parameters of physicochemical properties like weight variation, hardness of tablets, disintegration time, drug release study and assay.

Aim: To evaluate pain relief, anti-inflammatory and hypouricemic effects of GT1 tablets on experimental animals. Method: GT1 at the doses of 22.32 g/kg/day and 66.96 g/kg/day were evaluated for its analgesic effect in three models (hot plate, pain threshold, and acetic acid-induced writhing), its chronic anti-inflammatory effect in the granulomatous reaction model, and its hypouricemic effect in potassium oxonate-induced hyperuricemic mice. Acute anti-inflammatory effects of GT1 at the doses of 11.16 g/kg/day and 33.48 g/kg/day were evaluated in rats with two models: carrageenin-induced paw edema and peritonitis. Results: GT1 prolonged the temperature reaction time on the hot plate (22.73 s and 20.37 s at both doses of 22.32 g/kg and 66.96 g/kg, respectively, compared to 16.96 s in control group), reduced the number of acid acetic-induced writhing effects, decreased the weight of granulomas, and decreased the level of acid uric in blood and urine (p < 0.05). GT1 caused a significant reduction in paw edema after subplantar injection of carrageenan in rats (p < 0.05). Moreover, there was a substantial decline of GT1 at the dose of 11.16 g/kg/day in terms of the volume and the quantity of protein in the inflammation fluid of the peritonitis model (p < 0.05). Conclusion: GT1 at both doses of 11.16 g/kg/day and 33.48 g/kg/day posed acute anti-inflammatory effects on rats. GT1 at both doses of 22.32 g/kg/day and 66.96 g/kg/day exerted analgesic, chronic anti-inflammatory and hypouricemic effects on mice.

Objective: This study aimed to enhance the oral solubility and dissolution of poorly soluble lornoxicam by anti-solvent precipitation, and the manufacture of oral tablets by the phase transition method. Methods: The solvent was mixture of polyethylene glycol 400 and absolute ethanol. Three stabilizers Inutec SP1, Pluronic F127, Sucrose ester S1670 at two concentrations and two matrix formers Mannitol, and Avicel PH102 were used to obtain 12 formulae. The formulae were characterized regarding their infrared spectroscopy (IR), differential scanning calorimetry (DSC), particle size (PS) measurement, drug content and dissolution. Further characterizations were done for the optimum formula by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Four tablet formulae were manufactured by phase transition method. The optimum tablets (T3) were evaluated through hardness, drug content, disintegration, dissolution, IR, and stability studies. Finally, (T3) was compared to conventional tablets in New Zealand rabbits using crossover design. Results: The dissolution rate for the prepared formulae was enhanced, from 3.44 to 5.96 folds. Statistical significance was obtained using one and two way ANOVA among formulae. The optimum tablet formula (T3) had hardness 5.637±1.57 kg, drug content 90.424±1.19%, disintegration time 341.5±9.62 s and the drug dissolved 72.107±0.0025%. Stability, after one month storage of the selected tablets at (25 °c/60% relative humidity), was satisfactory. The absorption extent of lornoxicam from (T3) compared to the conventional tablets was higher. Conclusion: Taken together, the obtained results confirmed successfully the potential of the promising formula (T3), over the conventional tablets of lornoxicam.

Objective: Development of a rational composition, optimal technology, standardization criteria for tablets with Rheum cordatum extract, establishing the stability of the composition and storage conditions. Methods: As an active pharmaceutical substance, a standardized extract of Rheum cordatum was used. Pharmacopoeial excipients for the production of tablet mass are magnesium hydroxycarbonate, croscarmellose sodium, microcrystalline cellulose, Plasdone S-630, magnesium aluminum metasilicate, calcium stearate, purified water and film coating Opadry 85F18422 White. To obtain tablets qualified equipment was used in the technological process: a tablet mass mixer, a rotary tablet press, highly efficient film coating equipment, a packaging machine / blister machine. When developing the tablets, we were guided by the «Quality by design» concept of medicines, based on ICH guidelines: ICH Q11 «Development and manufacture of medicinal substances», ICH Q8 «Pharmaceutical Development» and ICH Q10 «Pharmaceutical Quality System». Standard pharmacopoeial research methods were used. Results: 50 experimental mass models for tableting have been developed in the variants of combining excipients and active substance in an effective single dose of 300 mg. Only 4 models of the core tablets obtained met the selection criteria (abrasion, crush resistance, disintegration, and dissolution). The optimal tableting method using wet granulation is substantiated, which makes it possible to obtain tablets of the proper pharmacopoeial quality and the following composition: soft rhubarb root extract, magnesium hydroxycarbonate, croscarmellose sodium, microcrystalline cellulose 102, Plasdone S-630, magnesium aluminum metasilicate, calcium stearate. To coat the obtained tablet cores, the following film coating composition was selected: Opadry 85F18422 White, consisting of polyvinyl alcohol, titanium dioxide E 171, macrogol 4000 and talc. Conclusions: The pharmaceutical development of coated tablets with an extract of Rheum cordatum has been done. The rational composition and optimal technology for producing tablet cores coated with a film coating of Opadry 85F18422 White were established. The quality of the obtained tablets was evaluated, the stability of the composition for 9 months was studied, the results of quality indicators are within acceptable standards, and research in this direction is going on. Keywords: Extract, coated tablets, pharmaceutical development, composition, technology, stability.

Background: Mesalazine (5-aminosalicylic acid, 5-ASA) is a drug substance with an antiinflammatory activity, which is mainly used in the symptomatic treatment of diseases, such as Ulcerative Colitis, the Crohn's disease and the idiopathic inflammatory bowel disease. Mesalazine exerts its effect locally in the inflamed area of the intestine and not through systematic absorption, therefore the investigation of its release characteristics from solid pharmaceutical formulations is of great importance. Objective: The development of novel mesalazine modified release formulations with improved properties, regarding drug release in the gastrointestinal tract, by utilisation of the Design of Experiments (DoE) approach. Methods: D-optimal experimental design was applied. A Simplex Lattice mixture design was used for the development of suitable capsules containing 4 mini tablets and a D-optimal mixture design was used for compression-coated tablets, with the following characteristics: ≤10% release in 2 h, to minimize its degradation in the upper gastrointestinal tract, 20-40% release in 5 h for mesalazine administration in the small intestine, and quantitative release in 12 h for colonic delivery. The dissolution experiments were conducted in gastrointestinal-like fluids and pectinases to simulate the pectinolytic enzymes present in the colon. Results: The optimal compositions were reached via the desirability function, as a compromise to the different responses. The optimal solutions for both formulations led to colon-specific delivery of the active substance with minimal 5-ASA release in the upper gastrointestinal tract and appeared to conform with the pre-determined characteristics. Hard gelatin capsules, when filled with mini-tablets led to the aimed modified release profile, having sigmoidal characteristics and compression coated tablets led to colonic delivery. Conclusion: Two novel mesalazine formulations were developed with the desirable colonic release, by conducting a minimal number of experiments, as suggested by DoE experimental design.

Conduct systematic analysis of the state of the supply of Ukraine with medications with chondroprotective activity. The Unified Clinical Protocol of Primary, Secondary (specialized) Medical Care allows doctors to control the state of a patient at every stage of illness and guarantees the effective treatment and prophylaxis of the locomotor system (LMS) pathologies.As a result of the chondroprotective medication range analysis it was determined that the pharmaceutical market of Ukraine is represented by 40 trade names of medications. The top market share of chondroprotective medications in Ukrainian market belongs to the foreign producers (52.5%), while domestic medications occupy 47.5%. In general the nomenclature of Ukrainian medications is provided by 6 manufacturing companies. Three pharmaceutical companies are the leaders producing 5 names of medications each (12.5% each): Pharmaceutical company “Zdorovye” (Kharkiv), PrJSC “Fitofarm” (Bakhmut, formerly Artemivsk, Donetsk region), JSC “Farmak” (Kyiv). Out of 40 trade names the medications are mainly produced: as coated tablets – 12 medications (30%), as solutions for injections – 11 items (27.5%), as capsules – 7 (17.5%), as soft dosage forms – 6 medicines (15%), and powders for oral administration – 4 items (10%).

This study presents optimization of a statistically based approach for setting up the dissolution test conditions for bisoprolol film-coated tablets using multivariate release models as predictive in vivo assessment tools for formulation behaviour. Additionally, the dissolution profiles of three different strengths of bisoprolol film-coated tablets were evaluated. According to the biopharmaceutics classification system, the tested medicinal product belongs to BCS Class I (high solubility, high permeability). Three dissolution media, including the dissolution medium of choice (pH 1.2) according to the USP monograph for bisoprolol tablets and two apparatus, paddle and basket were applied. The optimal conditions for performing the dissolution test were following: 900 mL of pH 1.2 as dissolution medium, apparatus 2 (paddle) with 75 r/min stirring speed. The quantity of the released active substance was determined using HPLC method. For a reliable statistical analysis, multivariate methods such as model-dependent approach coupled to multivariate statistics (Weibull), multivariate model-independent approach based on generalized statistical distance (Mahalanobis distance) have been applied for evaluation of dissolution profiles. All applied statistical approaches unequivocally support the underlying similarity of the pairs in different media between different strengths. Moreover, the optimized dissolution method has a discriminatory power to reflect the characteristics of the medicinal product in order to distinguish any changes related to quantitative composition of the formulation. Keywords: bisoprolol film-coated tablet, dissolution profiles, model-independent multivariate statistical distance, model-dependent multivariate statistical distance

A dissolution test for mianserin hydrochloride in coated tablets containing 30 mg was developed and validated using a fast ultraviolet spectrophotometric method. The appropriate conditions were determinate after testing sink conditions, agitation spped and dissolution medium. The sink conditions tested showed that mianserin hydrochloride was soluble in 0.01 and 0.1 M hydrochloric acid (HCl), acetate buffer pH 4.1 and 5.0 and phosphate buffer pH 6.8. Then, dissolution tests were performed to investigate the drug release in each medium. Optimal conditions to carry out the dissolution test were 900 mL 0.1 M HCl and USP apparatus 2 (paddle) at 50 rpm stirring speed. The quantification method was also adapted and validated. The UV method showed specificity, linearity, precision and accuracy. The in vitro dissolution test can be used to evaluate the drug release profile and the data was used as an aid to establish a possible correlation with in vivo data.

This study aimed to investigate the potential use of aqueous extract of Sorghum bicolor leaf sheath (SBLS) as a coating agent for paracetamol tablets. The mechanical properties of the coated tablets were assessed using crushing strength and friability test, while the release properties of the tablet were evaluated using disintegration and dissolution tests. The physicochemical properties of the coated tablets did not show any striking differences when compared with the uncoated tablet as par compendium specifications, which formed the basis for performing further in vitro dissolution study. Our data showed that SBLS enhanced the hardness and friability of the tablets in a dose-dependent manner. Tablets coated with 3, 5, and 7.5% of SBLS disintegrated in 8.13, 6.25, and 4.13 minutes, respectively, while the uncoated tablet disintegrated in 0.7 minutes. Furthermore, 3, 5, and 7.5% of SBLS-coated tablets exhibited slower release of their active ingredient (releasing 21, 16, and 17%, respectively) than that of the uncoated tablet (releasing 40%) in 5 minutes. Besides, comparison between the dissolution profiles was successfully achieved using difference factor (f1) and similarity factor (f2). The apparent dissimilarity between our coated tablets and the uncoated one led to further study of convolution in vitro–in vivo correlation, with the aim to obtain data that converted into mathematical prediction of in vivo data. For all batches, the percent predictable errors of C max and T max were within the acceptable limit of no more than 10%. In summary, SBLS aqueous extract is a potential and protective coat agent for paracetamol tablets. The in vitro established dissolution of the coated tablets provided scientific information for the prediction of the in vivo plasma drug profile.

In the present study to mask the unpleasant taste of chloroquine phosphate, hot melt coating technique was used as a taste masking tool. Hot melt coating is a solvent free technology grants rapid, additionally economical coating process with reduced risk of dissolving drug during process and provide uniform application rate of coating agent. Precirol ATO 5 was used as hot melt coating material for taste masking. Tablets were prepared by wet granulation method and coated using hot melt coating technique. Coated tablets exhibited good uniformity of drug content. Amount of drug release from all batches were evaluated. Taste evaluation of hot melt coated tablets was done by using electronic tongue.PrecirolATO5 was found to be a better taste masking agent when used by hot melt coating technique. Keywords: Precirol ATO 5, Hot melt coating, taste masking.

Objective: The objective of this work was to the development of natural and modified gum based sustained-release film-coated tablets containing poorly water-soluble drug. Methods: Tamarind seed gum (TSG), fenugreek seed gum (FSG), sodium trimetaphosphate, hydroxypropyl methylcellulose (HPMC), sodium alginate (SA), and nifedipine (NFD) were used. The core tablets of nifedipine were prepared and evaluated for weight, diameters, thickness, hardness, and disintegration time. The core tablets were coated using 2% w/v solution of TSG, MTSG, FSG, and MFSG. The in vitro release rate of drug from these coated tablets was compared with the release rate of drug from the tablets coated with 2% w/v of HPMC. Results: The tablets coated with natural and modified TSG sustained the release of the drug up to 11 h and 14 h, respectively, and natural and modified FSG sustained release the drug up to 9 h and 11 h, respectively. The tablets coated with HPMC sustained released the drug up to 15 h. The drug release profile of tablets coated with modified TSG was comparable to the release profile of tablets coated with HPMC. Conclusion: On the basis of the release profile, it is concluded that unmodified and modified TSG can be used as release rate-controlling membrane.

Dissolution testing of generic immediate release solid dosage forms represents a valuable tool to obtain dissolution profiles and to establish the similarity/dissimilarity between tested dosage forms. In this study, the in vitro dissolution profiles of generic immediate-release moxifloxacin (MOX) film coated tablets and a referent pharmaceutical product were compared and evaluated. The dissolution behavior of the generic product was investigated in three different dissolution media (pH=1.2, 4.5 and 6.8). The amount of dissolved MOX was determined using validated UV spectrophotometric method. For comparison of the dissolution behavior, the similarity factor, f2, was used. The dissolution profile of the generic product showed a release of >85 % MOX in the time frame of 30 min, in all the tested dissolution media. The similarity factor, f2, calculated from the comparison of the dissolution profiles of the generic and the referent pharmaceutical product in pH=1.2 dissolution medium was 50, 58, thus the products were established as similar. Based on the results of our study, the dissolution similarity between the generic MOX immediate-release film coated tablet and the referent product could be successfully used as a part of the approach to ensure their in vivo bioequivalence. Keywords: moxifloxacin, immediate-release solid dosage forms, dissolution, in vitro similarity

The aim of this study was to compare thein vitrodissolution behaviour of reference (R) and generic-test (T) medicinal products with non-linear effects model. Mathematical function Weibull, was employed as basis for the non-linear effects model, coupled with MATLABTMsimulation software to describe the release profile of the active substance. Medicinal products selected for the presented study include immediate-release tablets Concor 10 mg and Bisoprolol 10 mg, which belongs to BCS class 1 of biopharmaceutics classification system. The result from the study indicated that Weibull distribution function coupled with computer-based program is more useful for comparison of the dissolution profiles. This combined approach provides robust and informative results, with accurate estimation on thein vitroperformance for the medicinal products and it’s the most suitable tool for prediction ofin vivobehaviour of the medicinal product. In summary, we have employed Simulink graphical programming to design our system in a simulation environment.&nbsp

The objective of current research was to develop the models of dissolution prediction of tablets coated with cellulose acetate (CA 320S or CA 398-10) and cellulose acetate phthalate (C-A-P) blends. Independent variables selected were coating percent (X1) and percent of CA 320S or CA 398-10 (X2) in the blend. Dependent variables selected were dissolution in 1 (Y1), 8 (Y2), and 24 h (Y3). Diclofenac sodium core tablets were coated with blend of either CA 320S and C-A-P or CA 398-10 and C-A-P at approximately 5, 7.5, and 10% weight gain. CA 320S and CA 398-10 content in the corresponding blends varied from 33.3-66.7% and 25.0-50.0% relative to C-A-P, respectively. Dissolution was performed in phosphate buffer 6.8 using USP apparatus 2. Coated tablets were also characterized for surface morphology and coating uniformity by near infrared hyperspectroscopy. Y1, Y2, and Y3 were statistically (p < 0.05) affected by X2 in CA 320S/C-A-P and CA 398-10/C-A-P blends coated tablets. On the other hand, X1 had statistically significant (p < 0.05) effect only on the Y3 in CA 320S/C-A-P while Y1 was statistically (p < 0.05) affected by X2 in CA 398-10/C-A-P. Analysis of variance also indicated statistically significant (p < 0.05) effect of the studied variables on the dependent variables for both the blends. The models were verified by independent experiment. Model predicted and empirical values of Y1, Y2, and Y3 were close with maximum residual of 7.0%. In conclusion, dissolution can be modulated by varying composition of blend, polymer type, and coating weight.

Signal transformation (derivative and wavelet) was applied toUV spectra and ratio spectra to directly quantify spiramycin andmetronidazole in binary mixtures. Linear calibration graphs wereexamined for either drug in the concentration range of 6.25 – 25mg/L with R2 > 0.990. First derivative-transformed (i.e., usingSavitzky-Golay filter) and wavelet-transformed (i.e., using familiessuch as sym6, haar, db5, bior2.4, rbio2.4, meyr with scaling factor =256) UV spectrophotometric methods were statistically comparable tothe RP-HPLC reference method (p > 0.05) with regard to accuracyand precision when assaying spiramycin and metronidazole in theircoated tablets. These analytical methods used only green solvent, andproved to be time-saving and cost-effective.

The correlation between the high content of selenium (Se) in plasma and the low prevalence of cardiovascular disease has been published in previous epidemiological studies. The content of Se in the plasma is determined by daily intake. A preliminary surveillance of Se content of several plants showed that the seeds of jengkol (Pithecellobium lobatum Benth.) has the highest concentration of Se. This study aims to develop a pharmaceutical formulation of Se supplement for adjuvant therapy of cardiovascular disease. The jengkol seeds was made into film coated tablets with a wet granulation method. Optimization of the core tablet formula was carried out with variations of binder concentration and coating material. Evaluation was carried out on uniformity of size and weight, disintegration time, hardness and friability. The content evaluation was carried out including the levels of Se, water content, ash, fat, protein, carbohydrate and crude fiber. The results showed that the F3 had the lowest friability and highest hardness. The coating of tablets using PVA has covered the smell of jengkol seed. The evaluation results showed that film coated tablets contained the Se level content of 0.074 ± 0.004 µg/g, water content of 2.19%, ash content of 1.88%, fat content of 0.89%, protein content of 0.66%, carbohydrate content of 94.38% and crude fiber content 1.79%. The results showed that the jengkol seed film coated tablet formulation could be used as a supplement in additional therapy for cardiovascular disease.Keywords : Pithecellobium lobatum, film coated tablet, herbal supplement, selenium

The objective is to observe and improve drug release of Eplerenone which is BCS Class II API by applying dry granulation and wet granulation process. Inspra 50 mg film coated tablets, manufactured by Pfizer, were taken as reference product to compare with dissolution profiles of dry granulation applied product and wet granulation applied product. Investigation of the effect of wet granulation process on dissolution profiles of Eplerenone 50 mg film coated tablets has been demonstrated out in the scope the study. While f2 similarity factor is 44.93 for dry granulation applied product, it is 60.62 for wet granulation applied product when compared to reference product. It comply that dissolution rate of wet granulation applied product is more proper to the specification than dry granulation applied product. The study demonstrates the effect of different granulation process on dissolution rate.

The patient's sensory experience when taking an oral medicine is important in the assessment of its palatability, and acceptability. The aim of this study was to develop tools useful for standardisation of sensory assessment of coated tablets: a lexicon and a sensory wheel. Two randomised, double-blind sensory assessments were performed involving 83 and 52 heathy adult volunteers and two sets of coated tablets. By adapting the principles used by food sciences, a free-text description of conventional, bitter-tasting or tasteless, coated tablets was performed. In the first assessment, volunteers described the sensory attributes of the first set of tablets. The attributes collected were then validated using a second set of tablets in a separate study with different volunteers. The appropriateness and semantics of each sensory attribute was analysed. Twenty attributes most relevant for assessment of coated tablets were selected for the lexicon and associated with explicit definitions. A collection of all attributes that could possibly be triggered by coated tablets were organised in the form of a sensory wheel. This study provides a valuable insight into the sensory experience while taking a coated tablet and presents tools which can accelerate the development of palatable medicines.

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As per the Japanese or SUPAC guidance to maintain formulation composition similarity across tablet strengths, the coating should be applied based on the core tablet surface area or weight, respectively. These two coating approaches were compared by evaluating protective effects of coating on the light stability of three model compounds. Core tablets of three light sensitive drugs, nifedipine, rosuvastatin calcium, and montelukast sodium were coated either with PVA-based Opadry® II white or Opadry® II beige. The coated tablets were exposed to light up to three ICH cycles. For Opadry® II white, the surface area based coating provided consistent light protection across tablet strengths when the coating amount was more than 0.1 mg/mm2 compared to that based on core tablet weights. For Opadry® II beige, both approaches gave comparable and better light protection due to presence of iron oxides. The light protection by Opadry® II white could be because of physical barrier of coating, which was uniform across the strengths when it was based on core tablet surface area. For a routine tablet formulation development with Opadry color coating, it does not matter whether the coating is applied based on the core tablet surface area or weight.

There is great interest in demonstrating acceptability of solid oral formulations in paediatric populations. This study investigated the acceptability of small, 7.5 mm, bitter-flavoured, coated tablets in healthy children and adults. A randomised, double-blind acceptability test was performed involving 101 children (4–12 years) and 52 adults (18–75 years). Acceptability was measured by participants as sensory assessment of taste, mouthfeel and hedonic perception, and by researcher observations of ability to swallow the tablet and negative facial expressions. Additionally, the taste-masking effect of film coatings was assessed based on the intensity of bitterness perception. At least one tablet was voluntarily swallowed by 35.7% of 4–6-year olds, 74% of 7–12-year olds and 98% of adults. The bitterness of the tablet did not affect participants’ ability to swallow it. The sensory properties determined whether the tablet was acceptable. The following factors: low bitterness, high smoothness, high slipperiness and pleasant aftertaste had a positive impact on overall palatability in both populations. The paediatric scores during sensory evaluation of tablets differed from adults, showing lower acceptability. This study demonstrates the multifactorial nature of palatability of tablets and highlights that adults’ palatability evaluation cannot be directly translated to a paediatric population.

Minitablets are an appealing option for an age-appropriate pediatric dosage form. In particular, for combination therapies where multiple active ingredients are dosed simultaneously, the use of minitablets will enable independent adjustments of each dose. The work presented describes the development of Compound A and Compound B minitablets for a combination therapy. Since both actives are formulated as spray dried amorphous solid dispersions (ASDs) due to low solubility of their crystalline forms, the choice of minitablets for the pediatric dosage form allows the application of the same formulation strategy across different age groups. To address the potential need for taste-masking, an ethylcellulose-hydroxypropyl cellulose coating system was developed. In-vitro performance testing was conducted to guide coating development and to ensure proper taste-masking without slowing down API dissolution in the GI tract that can negatively impact exposures. As a result, the exposure of orally dosed coated tablets was comparable to those of uncoated minitablets in the canine model. The work presented can serve as a case study on how minitablets can be designed and developed as an appropriate pediatric dosage form for a combination therapy comprised of ASD of active ingredients.

Modified release of furosemide from tablet formulations is preferred by patients, because of physiological problems, acute diuresis being the most serious, compared to the forms designed for immediate release. With this in view, we aimed at achieving furosemide’s longer gastric retention and waste minimization by preparing matrix and compression coated tablets incorporating different grades of Eudragit® and poly(ethylene oxide) (PEO), polyvinylpyrrolidone (PVP) and lactose monohydrate. Dissolution profiles of the new formulations were compared with that of the main stream drug Lasix®, 40 mg tablets. The results indicate that the use of Eudragit® in conjunction with either PVP or lactose monohydrate led to a slower release rate in the intestinal fluids compared to Lasix®. Moreover, furosemide release in the intestinal pH from matrix tablets and compression coated tablets was not noticeably different. Formulations incorporating PEO led to sustained release, in intestinal fluids, which depended on the molecular weight of PEO.

This work aimed to map and discuss tablet-coating choice, quality deviations of this process, and corrective actions taken by Research and Development (R&D) teams from pharmaceutical industries. A cross-sectional study of polymeric film coating was conducted in Brazil: a questionnaire based on literature information was sent to R&D divisions from several different companies that produce coated tablets in the country, which focused on the main type of coating systems used, most common quality issues, corrective action to each nonconformity, and the main influences in the choice of the coating system. The most used film coating systems are hydroxypropylmethylcellulose + Polyethylene glycol (HPMC/PEG) and polyvinyl alcohol + PEG (PVA/PEG), and the most common non-conformities are orange peel, picking sticking, chipping, and peeling. The main suggestive corrective actions include temperature control, pan speed, spray, and pressure rate. All results were analyzed by us according to literature and authors’ expertise. Finally, stability was the main factor that influences the selection of a coating system. These data brought knowledge on routine industrial practices, when real deviations happen and matter, with no reports found in the literature.

This study aimed to determine the compliance between the actual levels of vitamins A, C, and E, determined by laboratory analysis, with those declared on the labels of vitamin supplements sold in an urban area in Brazil. Fifty-seven samples of vitamin supplements (tablets, sugar coated tablets, hard and soft gel capsules, suspensions, and solutions) were evaluated to determine their antioxidant vitamin contents. Vitamin A, E, and β-carotene contents were determined by high-performance liquid chromatography with diode-array detection (HPLC-DAD), and vitamin C content was determined by automatic potentiometric titration. Of the samples analyzed, 71% and 50% had lower vitamin A and E content, respectively, than the declared values. In contrast, 28% of the analyzed samples had vitamin E content greater than the declared value. The vitamin C content of 67% of the samples was consistent with the declared value. Some supplements analyzed had vitamin content ranging from “not detected” to 81% higher than that reported on the label. The wide variability observed between the stated label amounts of vitamins and those determined analytically demonstrates the need for control measures and enforcement actions to ensure that consumers have access to safe and reliable information about vitamin supplements.

The purpose of this study was to develop and validate a discriminative dissolution method for the metformin film-coated tablet with immediate release of the active substance that belongs to class III of the Biopharmaceutical Classification System (BCS). Different conditions such as type of dissolution medium, volume of dissolution medium, rotation speed, apparatus, and filter suitability were evaluated. The most discriminative release profile for the metformin film-coated tablet was accomplished by using Apparatus II (paddle) and 1000 mL of phosphate buffer pH 6.8 as the dissolution medium and maintained on 37 ± 0.5°C with a rotation speed of 75 rpm. The quantification of the released active substance was performed by UV/Vis spectrophotometry, at 232 nm. Acceptance criteria for not less than 75% (Q) of the labeled content for 45 minutes were set. The dissolution method was validated according to the current international guidelines using the following parameters: specificity, accuracy, precision, linearity, robustness, and stability of the solutions, found to be meeting the predetermined acceptance criteria. A developed dissolution method has discriminatory power to reflect the characteristics of the medicinal product and is able to distinguish any changes related to quantitative formulation and can be also applied for routine batch testing.

OBJECTIVE To compare real-world adherence to and persistence with deferasirox film-coated tablets (DFX-FCT) and deferasirox dispersible tablets (DFX-DT) among patients who switched from DFX-DT to DFX-FCT, overall and by disease type (sickle cell disease [SCD], thalassemia, and myelodysplastic syndrome [MDS]). METHODS Patients were ≥2 years old and had ≥2 DFX-FCT claims over the study period and ≥2 DFX-DT claims before the index date (first DFX-FCT claim). The DFX-DT period was defined from the first DFX-DT claim to the index date; the DFX-FCT period was defined from the index date to the end of the study period. Adherence was measured as medication possession ratio (MPR) and proportion of days covered (PDC). Persistence was defined as continuous medication use without a gap ≥30 or 60 days between refills. Comparisons were conducted using paired-sample Wilcoxon sign-rank and McNemar's tests. RESULTS In total, 606 patients were selected (SCD: 348; thalassemia: 107; MDS: 106; other: 45). Adherence and persistence in the DFX-FCT vs DFX-DT period was significantly higher across all measures: mean MPR was 0.80 vs 0.76 (p

The pharmacokinetics, bioequivalence, and safety of Femorix® (Valenta Pharm Co., Russia) and Aubagio® (SanofiWinthrop Industrie, France) film-coated tablets (14 mg) were compared in a double-blind randomized investigation in parallel groups of healthy volunteers. The bioavailabilities of Femorix® film-coated tablets (14 mg, Valenta Pharm Co., Russia) were 96.18% [87.92 – 105.22%] for ln(Cmax) and 96.24% [88.67 – 104.44%] for ln(AUC0–72) of those for Aubagio® film-coated tablets (14 mg, Sanofi Winthrop Industrie, France), which fell in the commonly accepted range (80 – 125%) for proving the bioequivalence of the tested products.

This study was conducted in order to compare the bioavailability of two film-coated tablets containing 25 mg of quetiapine.24 subjects were enrolled in and completed a single-center, randomized, single-dose, open-label, two-way crossover study with a 1-week washout period. Plasma samples were collected up to 24 hours following drug administration; thus, quetiapine was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with turbo-ion-spray mode. The pharmacokinetic parameters used for bioequivalence assessment were AUCsub0-t/sub, AUCsub0-∞/sub, and Csubmax/sub. The 90% confidence intervals were obtained by analysis of variance for AUCsub0-t,/subAUCsub0-∞/sub, and Csubmax/sub.The results were all within the range of 80.00 - 125.00%.Bioequivalence between formulations was concluded both in terms of rate and extent of absorption. .

The aim of this work was to develop zein-based press coated tablets for delayed, time-controlled drug release. Press coated tablets containing dextrates and chlorpheniramine maleate (BCS class 1 drug) in the core, and zein and either NaCl, sodium starch glycolate (SSG) or crospovidone (XPVP) in the coat were produced. Results show that tablets containing zein and NaCl in the coating could not release nearly any drug over 8 h. On the contrary, when SSG and XPVP were incorporated at a level of 8 % in the coating, a delayed drug release pattern was obtained, characterised by a lag-time of 3 h, followed by a burst of >80 % drug release over 6–7 h. Drug release was dependent on the concentration of SSG and XPVP in the formulations. Images of the tablets showed that during the lag-time the dosage forms did not change shape, although they started to swell. After this time, tablets gradually deformed and eventually ruptured. The lag-time is due to the time needed for the water to diffuse in, for the drug to dissolve and for the coating to become sufficiently permeable. The addition of the hydrophilic and swellable superdisintegrants SSG and XPVP to zein shifted the hydrophilic/hydrophobic balance of the coatings to higher hydrophilicity, thus enabling rapid hydration and drug release after the lag-time. This study demonstrates that zein-based macroscopic drug delivery systems can be tuned to tailor drug release to specific needs, i.e. delayed release in this case.