Effervescent Formulation Research Articles

Controlled Release Bilayer Floating Effervescent and Noneffervescent Tablets Containing Levofloxacin and Famotidine

The present study is aimed at designing bilayer-floating tablets to improve the drug concentration in the stomach for enhanced therapeutic efficacy. The tablets are comprised of an upper layer of levofloxacin (466.5 mg) and a lower layer of famotidine (133.5 mg). Five formulations (F1-F5) were developed by using hydroxypropyl methylcellulose grades (K4M, K15M, and K100M) along with Carbopol 934. In the case of the effervescent system (F1-F3), sodium bicarbonate was added to impart buoyancy to the tablets; while in the case of noneffervescent formulations (F4 & F5), guar gum and xanthan gum were incorporated to induce flotation and swelling and retard the release of a drug. The precompression characteristics of tablets depict the suitability of all formulation powder for direct compression. The ATR-FTIR analyses have shown that the components of both effervescent and noneffervescent tablets are compatible with each other. The total weight of each tablet was 600 mg, with a weight variation of about ≤10 mg. Both the layers were smooth and flat with a thickness ranging from 3.16±0.04 to 3.54±0.01 mm. The diameters of prepared floating tablets were about 15 mm, optimum for oral administration. After adjusting the tablet’s hardness to 6-7 kg/cm2, its friability was found to be <0.35 percent. The mean drug content of the formulations was above 90%. The floating lag time of all formulations (F2-F5) was below 25 seconds, except F1 which took almost 50 seconds to start floating on the surface of gastric content due to its higher density. The total floating time of effervescent (F1-F3) and noneffervescent formulations was in the range of 15-25 hours, thereby providing sufficient time to complete drug release and absorption in the gastric area. The total floating time of noneffervescent formulations was higher (p≤0.05) than effervescent formulations due to efficient wettability and swelling characteristics. The release of drugs from both layers of noneffervescent tablets was significantly controlled when compared to the effervescent system, and an anomalous non-Fickian diffusion was found for the drug release. The stability study of the optimized formulation proved the integrity and stability of the developed formulation. Thus, developed formulations are deemed suitable for controlled codelivery of active pharmaceutical ingredients for the effective treatment of H. pylori.

Effervescent Formulation of Oil Palm Leaf Extract as a Free Radical Scavenger

Non-communicable diseases have become the leading cause of death in Indonesia, accounting for approximately 69% of deaths in 2023. Various health disorders, such as cancer, neurodegenerative diseases, inflammation, hypertension, and heart disease, are linked to oxidative stress caused by reactive oxygen species (ROS). Chemical treatments often have side effects and high costs, prompting many to turn to natural remedies. One preventive measure against ROS is consuming natural foods rich in antioxidants, such as oil palm leaf extract. This study uses the roller slugging compaction method to transform oil palm leaf extract into effervescent tablets. Palm oil leaf extract has been prepared in 2 different sources ( 1st and 17th leaf) to assess percent inhibition. The experimental results showed that the 17th leaf extract had the highest antioxidant activity value (IC50 = 20.35). Then, the 17th palm oil leaf extract was used in effervescent tablet formulations. The results obtained indicate that formulation 1, consisting of 0.5 grams of oil palm leaf extract, 0.195 grams of citric acid, 0.2925 grams of tartaric acid, 0.4875 grams of NaHCO3, 0.975 grams of maltodextrin, and 0.05 grams of PVP, is the best formula for oil palm leaf extract effervescent tablets. This formulation demonstrated the highest antioxidant activity (IC50 = 30.22), consistent with its total phenolic content (394.451 mg GAE/mL).

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality.

Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non-sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. A total of 460 980 and 14 462 patients were identified for the non-sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference -0.04 mmHg (95% confidence interval -0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice.

Lemongrass Powder in Bio-Bs Effervescent Formulation of Lombok Island Local Isolate on Viability and Amount of Bacillus Sphaericus Toxin Crystal Protein for Control of Anopheles sp. Larvae

Bio Formula – BS effervescent (Bio- Bacillus sphaericus) is an Effervescent powder-shaped formula that is easy to use by the public. Lombok's local effervescent bio-BS isolated formula has a weakness in terms of smell. The results from the literature search that fragrant lemongrass has a distinctive smell and can kill Aedes aeygpti, but scientific data has not been obtained about the ability of fragrant lemongrass to kill Anopheles Sp in the form of larvae and mosquitoes. The study aimed to find out the effect of the combination formulation of Bio-BS Effervescent local isolate Lombok Island with the addition of lemongrass powder for viability and the amount of toxin crystal protein Bacillus sphaericus. This research method is exploratory and experimental in the laboratory with the design of Post Test Only Control Group Design. The study used six treatment formulations. Samples of Anopheles sp larvae research in Batu Layar lagoon, West Lombok regency and pelur lagoon in Peringgesela, East Lombok regency and from the results of colonization of larvae. The independent Variable is a combination formulation of Bio-BS Effervescent isolated locally from Lombok Island with the addition of fragrant lemongrass powder. The dependent variable is the mortality of Larvae Anophels Sp, Viability of B. Sphaericus, and Amount of Toxin Protein Production of B. Sphaericus. The larvae death rate, the concentration of cells/endospores, and the number of repeats in each container are then tabulated and analyzed using Probit Analysis with the help of MINITAB 16 software. B. sphaericus viability data and the amount of endospore toxin protein crystal production were descriptively analyzed.

Determination of Simethicone by Gravimetric Analysis from Effervescent Formulation

Determination of Simethicone by Gravimetric Analysis from Effervescent Formulation

Preparation and Evaluation of Diclofenac Sodium Effervescent Tablet

The oral dosage forms are the most popular way of taking medicine although having some disadvantages like deliberate absorption and thus onset of action is extend. This can be overcome by administrating the drug in a liquid form i.e. effervescent tablet. The research is a formulation of diclofenac sodium as a effervescent tablet by wet granulation method. The bitter taste of the drug are masked by added sweetening agent (lactose, glucose etc.) In the present work we are prepared effervescent tablet in that we are used active drug diclofenac sodium and other active ingredient acid like tartaric acid and base sodium bicarbonate in different concentrations. The formulation of tablet was done by using wet granulation, wet granulation is found to be acceptable method of effervescent tablet formulation. The various pre-formulation studies was performed hardness, weight variation, disintegration, dissolution etc.

Comprehensive Review on Ficus Deltoidea Effervescent Mouthwash Formulation in Treating Oral Pathogens

Ficus deltoidea or its well-known local name Mas Cotek belongs to the family of Moracaeae. This native plant is commonly found in Malaysia, other tropical and subtropical countries. Oral periodontal disease is an alarming disease and the utilization of herbal plants in treating oral pathogens has raised attention and concern. Therefore the main objective of this study was to review the effectiveness of effervescent mouthwash formulation of the FDL on treating oral pathogens. Plaque accumulation and oral microorganisms are the main predisposing factors to oral periodontal diseases. Herbal mouthwash has been of particular interest these days to treat oral pathogens. Different effervescent agents such as citric acid, tartaric acid, and sodium bicarbonate were used in formulating effervescent mouthwash by different methods with varying concentrations. FDL leaves have claimed to possess different properties such as antioxidant, anti-diabetic, and anti-inflammatory properties which are helpful in treating many diseases. Post compression parameters such as effervescent time, moisture content, and in vitro antibacterial test were reviewed in this study. FDL has shown a strong correlation to the presence of high content of polyphenols, flavonoids, saponin, tannins, and triterpenoids. In conclusion, the type of preparation choosen is by using wet granulation method and the suitable ratio is 2:1.

COMPARATIVE ANALGESIC EFFECTS OF SINGLE-DOSE PREOPERATIVE ADMINISTRATION OF PARACETAMOL (ACETAMINOPHEN) 500 mg PLUS CODEINE 30 mg AND IBUPROFEN 400 mg ON PAIN AFTER THIRD MOLAR SURGERY

Efficacy and rapid onset of postsurgical oral pain relief are critical to improve clinical outcomes and reduce the risk of excessive dosing with analgesic drugs. To compare analgesic effects of preoperative administration of paracetamol 500 mg plus codeine 30 mg in single-tablet and effervescent formulation to ibuprofen 400 mg, and placebo in the management of moderate to severe postoperative pain after mandibular third molar surgery. One hundred twenty healthy outpatients aged 15-29 years undergoing surgical removal of 1 bony impacted mandibular third molar were enrolled in this, single-center, prospective, randomized, triple-blind parallel-group, placebo-controlled, clinical trial. Study participants were randomly assigned to three treatment arms. According to the concealed allocation, each patient 30 minutes before surgery received paracetamol 500 mg plus codeine 30 mg (group APAP/COD), ibuprofen 400 mg (group IBU) or placebo (group PLA). Rescue therapy allowed in the postoperative period was paracetamol 500 mg plus codeine 30 mg in groups APAP/COD and PLA and ibuprofen 400 mg in group IBU. Patients recorded on Numerical Rating Scale-11 (NRS-11) the pain intensity, total number of postoperative-supplement medications and time of the first intake, until 12-hours after surgery and over extra 2 days, RESULTS: Over postoperative 3 days, patients in the APAP/COD group (2.33 ± 1.99) displayed significantly (P< .001) less pain intensity than IBU (3.43 ± 2.47) and placebo (3.57 ± 2.62) groups. The first-day postoperative pain was significantly (P < .001) higher in group PLA than in groups APAP/COD and IBU, but not between the latter 2 groups. However, at 2 hours postdose, the IBU group displayed average pain intensity lower than APAP/COD group (P> .05). On the next 2 days, pain intensity was significantly (P< .001) lower in group APAP/COD than in groups IBU and PLA but failed to reach statistical significance between groups IBU and PLA. Although the time to the first using rescue therapy was longer (445.88 ± 159.96 minute) in group IBU, compared to groups APAP/COD (392.67 ± 138.90 minutes) and PLA (323.00 ± 143.95 minutes), the number of supplemented tablets was significantly higher in group IBU (2.89 ± 2.13) than in groups APAP/COD (1.24 ± 1.79) (P= .001) and PLA (1.53 ± 1.67) (P = .008). No adverse events were registered for all groups. Within the limits of the present study, over postoperative 3 days, a statistically significant intensity pain reduction and decreased rescue therapy consumption were recorded in the paracetamol-codeine group than to ibuprofen group. Nevertheless, lower pain intensity at 2 hours postdose and longer time using rescue therapy was found in the ibuprofen group without statistical significance. No adverse events occurred over the studied period.

Quantification of carbon dioxide released from effervescent granules as a predictor of formulation quality using modified Chittick apparatus

Purpose: To develop a method for the measurement of carbon dioxide (CO2) released from effervescent formulations.&#x0D; Methods: Effervescent granules were prepared using sodium bicarbonate and citric acid by fusion and solvent-assisted granulation methods. The amount of CO2 released was determined from the maximum pressure of gas release, time profile of pressure gradient using modified Chittick apparatus and gravimetric changes following effervescence.&#x0D; Results: The amount of CO2 released from effervescent granules prepared by fusion method was 8.125, 8.763 and 7.98 mM/g measured by ideal gas equation, pressure gradient and gravimetric method, respectively. The formulation prepared by solvent-assisted granulation showed 5.525, 5.475 5.36 mM/g of carbon dioxide measured by the above three methods, respectively. The effervescent granules prepared by fusion method showed approximately 2 % loss in effervescence. However, approximately 39 % loss in effervescence was observed for the formulation prepared by solventassisted granulation. The commercial products showed a loss in effervescence in the range of 5 - 15%.&#x0D; Conclusion: Modified Chittick’s apparatus is a useful analytical tool for monitoring of the CO2 from effervescent granules as a function of method of preparation.

Effervescent formulation based on variation of nanocapsules matrix type and roselle (Hibiscus sabdariffa) nanocapsules percentage

Roselle flowers are usually consumed in the form of fresh steeping. To increase the flexibility of using roselle, effervescent roselle-based products are made which of course more practical, efficient and attractive. Unfortunately, the bioactive compound in roselle extracts is not stable to environmental influences so nanoencapsulation technology needs to be done. The encapsulation matrix type gives a unique effect on each core. The purposes of this study were to determine the effects of variation in the matrix types and percentage of roselle nanocapsules on the physical and chemical effervescent properties. The research design used in this study was a Complete Random Design with 2 factors and 3 replications. The first factor comprised matrix types (A): maltodextrin (A1) and Arabic gum (A2). The second factor was roselle nanocapsule percentages (B): 10% (B1), 15% (B2) and 20% (B3). Observed variables in this study were total phenol, anthocyanin, vitamin C, antioxidant activity and dissolving time. The Arabic gum nano encapsulated matrix type gave a better value of Vitamin C, antioxidant activity and dissolving time than maltodextrin, namely 0.149±0.049 µg/3 g, 34.02±4.52%, 2.93±0.80 mins. The percentage of roselle nanocapsules by 20% gave the highest vitamin C value, namely 0.188±0.032 µg /3 g. The best treatment combination was obtained from the treatment (A2B3) Arabic gum nanocapsules using the third percentage (20%) with the characteristics: total phenol content 4.17 µg /3 g, anthocyanin 0.070 µg /3 g, vitamin C 0.188 µg /3 g when it dissolves in 1.25 mins.

Phytochemical Screening, Spectrum Profile of Functional Groups, and Effervescent Formulation of Kepok Banana Peels Stem Extract

Kepok banana plants contain secondary metabolites such as tannins and flavonoids. Tannins and flavonoids have various properties for human health. Research has been carried out to identify secondary metabolite compounds (tannins, flavonoids, and saponins) by using the phytochemical screening method to see the functional group profile contained in the extract of kepok banana stem waste. Kepok banana stem waste was extracted in 96% ethanol, then evaporated and screened phytochemically. This extract was used to prepare effervescently. Screening results showed that tannin and flavonoids were identified by the appearance of the following color black-green and dark red, respectively. Meanwhile, saponins were negative because the foam formed had a height of 0.3 cm and did not meet the saponins' positive requirements (1-3 cm high foam and stable for 5 minutes). Identification of functional groups in the extract of kepok banana stem waste using Fourier-transform Infrared Spectroscopy (FTIR) showed that C-C stretching in the area 2927.24 cm-1, O-H stretching in the 3423.87 cm-1 area, C=O stretching in the 1648.87 cm-1 area. Also appeared bending CH2 in the region of 1421.45 cm-1, and C-C in the area of 1149.98 cm-1. The characteristics of three different formulas (A, B, and C) of effervescent have been investigated: the moisture content of 2.51%; 2.55%, and 2.52%, respectively. Then, flow rate of 8.81 g/s; 8.83 g/s; and 8.82 g/s, compressibility of 14.5%; 14.4%; and 14.5%, and a pH of 5.97; 5.98; and 5.97 respectively. All parameters are eligible.

A novel effervescent formulation of oral weekly alendronate (70 mg) improves persistence compared to alendronate tablets in post-menopausal women with osteoporosis

BACKGROUND A novel effervescent buffered solution of 70 mg alendronate (ALN-EX) was developed to improve upper gastrointestinal (GI) tolerability over alendronate tablets (ALN-T). Whether a better GI tolerability can improve persistence remains to be determined. AIM This study evaluated persistence and reasons for discontinuation in patients treated with ALN-EX compared to a historical cohort on ALN-T. METHODS Post-menopausal women (PMW) from a standardized clinical database with BMD T-score < -2.5, or between -2 and -2.5 and at least one vertebral fracture, starting ALN-EX between July 2015 and June 2016 were included. A historical cohort comprised of randomly selected and age-matched PMW on ALN-T was used as a control. Persistence at 6 and 12 months and reasons for discontinuation (e.g. adverse events; AE) were compared between the two groups. RESULTS A total of 144 PMW on ALN-EX and 216 PMW on ALN-T were analysed. Persistence at 6 and 12 months was 91% and 81% in the ALN-EX group vs. 75% and 69% in the ALN-T group, this difference attaining statistical significance at both 6- (p < 0.001) and 12 months (p = 0.009). A significantly higher proportion of patients receiving ALN-T discontinued treatment due to GI AEs (4% ALN-EX vs. 11% ALN-T; p = 0.027), or patient's decision to discontinue (6% ALN-EX vs. 13% ALN-T; p = 0.016). The adjusted odds ratio of persisting on ALN-EX treatment at 12 months was 2.02 (95% CI: 1.21-3.41, p = 0.008). CONCLUSION Our findings demonstrate that ALN-EX can provide greater persistence and improved tolerability compared to ALN-T, allowing it to be a viable alternative option in the management of osteoporosis.

Application of response surface methodology (RSM) in statistical optimization and pharmaceutical characterization of a patient compliance effervescent tablet formulation of an antiepileptic drug levetiracetam

BackgroundThe main objective of the present study was to develop and optimize an effervescent tablet of levetiracetam, an antiepileptic drug, using central composite design with response surface methodology (RSM).The present investigation helps to overcome the problem associated with levetiracetam tablets and liquid dosage forms with children and elderly people like bad taste and swallowing difficulties. It also facilitates as an alternative manufacturing process for advanced patented technology like 3D printing process employed in SPRITAM® tablet.Levetiracetam effervescent tablets were prepared by dry granulation (roll compaction) method using water-soluble excipients and optimized by central composite rotatable design (CCRD) using two variables (citric acid and effersoda) at two levels (high and low). Overall, fourteen formulation trials were generated through statistical software Minitab 17.3.0 placing 6 center points, 4 cube points, and 4 axial points. All formulations were subjected to compression using single punch machine.ResultsQuality attributes of compressed tablets were evaluated using various compendial and non-compendial tests. RSM was used to observe the responses like effervescent time, hardness, and friability of the prepared tablet batches for different levels of all the variables. Polynomial equations were developed, and model plots (contour plot and 3-dimensional model surface plots) were generated to study the impact of acid-base couple on the responses. Finally, the optimized formulation was selected on the basis of desired effervescent time, hardness, friability, percent drug release, and drug content. From the studied RSM design, it was observed that small changes in the independent variables (citric acid and effersoda) correlate with shifts in the dependent variables, i.e., the desired responses. The study reveals that all the independent variables (citric acid and effersoda) and dependent variables (effervescent time, hardness, and friability) have a good correlation as indicated by good linear regression coefficient of 0.9808, 0.9939, and 0.9892 for effervescent time, hardness, and friability respectively.ConclusionLevetiracetam effervescent tablets are satisfactorily prepared by dry granulation (roll compaction) approach. All desired critical quality attributes were found to be satisfactory. The applicability of RSM with desirability function in optimizing the levetiracetam formulation has made it possible to identify the impact of various independent variables and explore their effect on required responses.

Bursting bubbles for better bioavailability

An effervescent formulation increases the oral bioavailability of hard-to-solubilize hydrophobic and hydrophilic chemotherapeutics.

Optimization of Taste-Masked (-)-Oleocanthal Effervescent Formulation with Potent Breast Cancer Progression and Recurrence Suppressive Activities.

S-(–)-Oleocanthal (OC), a naturally occurring phenolic secoiridoid exclusively found in extra-virgin olive oil (EVOO), is a potential nutraceutical therapeutic for inflammation, neurodegenerative diseases, and many malignancies, especially breast cancer (BC). The oral delivery of OC is challenging because of its irritative, bitter, and pungent taste and exceptional chemistry, including two reactive aldehydes, phenolic, and ester groups. OC irritation did not correlate with CO2-induced irritation, and hence, OC was not exerting generalized acid-sensing irritation. The objective of this study was to develop an effervescent formulation of OC with an effective CO2-induced masked taste maintaining the efficacy against the estrogen receptor (ER) and HER2 positive BC. Several ratios of acid and carbonate sources were screened, and five effervescent formulations EF1-EF5 were selected and prepared based on their pH and effervescence time. OC formulations were characterized using differential scanning calorimetry, FT-IR spectroscopy, and scanning electron microscopy analyses. OC formulations exhibited acceptable flowability and effervescence time. Based on physical characteristics and improved OC release, formulation EF-2 was selected for subsequent studies. EF-2 showed effective OC taste masking, as suggested by electronic artificial tongue and mouse preference tests. EF-2 suppressed more than 70% of the hormone and HER2-positive BT-474 BC cell growth in a nude mouse xenograft model. Furthermore, EF-2 demonstrated significant inhibition of BT-474 tumor cell locoregional recurrence after primary tumor surgical excision. EF-2-treated mouse sera had significantly reduced CA 15-3 levels, the human BC recurrence marker, compared to the placebo control group at the end of the study. These results highlight the potential of the OC formulation EF-2 as a prospective nutraceutical for the control and prevention of ER+/HER+ BC progression and locoregional recurrence.

A Novel Ultra-High Performance Liquid Chromatography Method for the Determination of Erdosteine, Related Impurities and Degradation Products in New Effervescent Tablets

A novel and automated, stability-indicating, reversed phase ultra performance liquid chromatography (UPLC) method was developed and validated for the quantitative determination of erdosteine, its known impurities and two novel degradation products in a new pharmaceutical dosage form (effervescent tablets). The chromatographic separations were performed on a Waters Acquity UPLC HSS T3, 1.8 µm (2.1 mm × 150 mm, I.D.) stainless steel column. The mobile phase consisted of 0.1% TFA in water and methanol under gradient elution conditions, at a flow rate of 0.29 mL/min, for the assay and impurities analysis. UV detection was set at a wavelength of 238 nm. Erdosteine raw material, placebo and effervescent tablets were subjected to forced degradation. The new degradation products (labeled OX1 and OX2) were found after oxidative treatment and characterized by ultra performance liquid chromatography mass spectrometry. The validation parameters such as linearity, limit of detection (LOD) and quantification (LOQ), accuracy, precision, specificity and robustness were highly satisfactory for all analyzed compounds. LOD (0.020 and 0.011–0.385 µg/mL for erdosteine and impurities, respectively) and LOQ values show the high sensibility of the method. Specificity of the method was confirmed by testing the matrix components. The validated method demonstrated to be suitable for routine quality control purposes and for routine stability studies of erdosteine in effervescent formulations.

Development and Validation of an Analytical Method for Related Substances in N-acetyl–L-cysteine Effervescent Tablets by RP-HPLC

Background: The reported chromatographic methods for N-acetyl cysteine [NAC] are reverse phase HPLC and ion pair chromatography [IPC] for related substances test in bulk and in formulations. No reported stability indicating methods for the estimation of related substances in NAC effervescent formulation was found in literature. Objective: The present work was aimed at developing a selective, sensitive and reproducible stability indicating high-performance liquid chromatographic method for the quantitative determination of known, unknown impurities, degradation impurities and processrelated impurities of NAC effervescent formulation. Method: A reversed phase ion pair chromatographic method was developed employing Cadenza C18 column as the stationary phase and 0.01M octane sulphonate [pH 2.20], methanol and acetonitrile in the ratio 90:8:2 as the mobile phase. A gradient programme was followed with a run time of 55 minutes. 0.3 M hydrochloric acid was selected as the optimum diluent. The performance of the method was validated according to the ICHQ2R1 guidelines. Results: The method was found to be linear from 1.5 to 25μg/ml for impurities A, C and D and from 2.0 to 25 μg/ml for impurity B. The official impurities C and D were mapped in all stress conditions. Additionally, impurity B was also seen in acidic conditions. Conclusion: The results from the study demonstrate that the method is suitable for evaluating the stability of NAC effervescent tablet.

Effect of directly compressible excipient and treated agar on drug release of clopidogrel oral disintegrating tablets.

In the present investigation, oral dissolving/dispersible/disintegrating tablets (ODTs) of clopidogrel were designed with a view to enhance the bioavailability and patient compliance by two different methods, namely, direct compression and effervescent methods using directly compressible excipient and treated agar (TAG). In the direct compression method, TAG was used as a disintegrant and another method used a mixture of sodium bicarbonate and tartaric acid along with TAG as disintegrants. Among the directly compressed tablets, treated agar formulation 3 and among the effervescent tablets, treated agar and effervescent formulation 4 was found to be promising. Treated agar formulation 3 prepared by direct compression method emerged as an overall best formulation based on the in vitro drug release characteristics.

Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation

SummaryNo clinically important pharmacokinetic interference of alendronate occurred between a new effervescent formulation of alendronate and levothyroxine when coadministered. The combination does not materially affect levothyroxine absorption.IntroductionConcurrent treatment of osteoporosis with alendronate (Aln) and hypothyroidism with levothyroxine (LT4) may be problematic because both drugs are to be taken separately after fasting overnight. The primary objective was to assess pharmacokinetic interactions between a new effervescent formulation of Aln (Aln-NEF) and LT4.MethodsA randomized, open-label, 3-way crossover study was conducted in 30 healthy adults (15 women). Subjects were dosed 3 times, separated by 35 days, after overnight fasts, with Aln-NEF alone (70 mg), LT4 alone (600 μg), or Aln-NEF and LT4 concurrently. Samples were analyzed for plasma Aln and serum LT4. Pharmacokinetic drug-drug interaction was assessed using 90% confidence intervals (CIs) for the test/reference ratio of the geometric means for area under the concentration-time curve from time zero to last measureable time point (AUC0-t) and maximum concentration (Cmax). Results were compared to the default no-effect boundaries of 80 to 125% for the ratio Aln-NEF and LT4 concurrently/Aln-NEF alone and the ratio Aln-NEF and LT4 concurrently/LT4 alone.ResultsGeometric mean ratios (Aln-NEF with LT4/Aln-NEF alone) were 0.927 (90% CI 0.795–1.081) for AUC0–8 and 0.912 (90% CI 0.773–1.077) for Cmax, demonstrating LT4 does not appreciably affect the pharmacokinetics of Aln. Geometric mean ratios (LT4 with Aln-NEF/LT4 alone) were 1.049 (90% CI 0.983–1.119) for AUC0–48 and 1.075 (90% CI 1.006–1.148) for Cmax, demonstrating LT4 is bioequivalent between the 2 treatments. Coadministration of Aln-NEF and LT4 was well tolerated.ConclusionsThere was no clinically important pharmacokinetic interference between the Aln-NEF formulation and LT4. Aln-NEF does not materially affect LT4 absorption.

Solid effervescent formulations as new approach for topical minoxidil delivery

Currently marketed minoxidil formulations present inconveniences that range from a grease hard aspect they leave on the hair to more serious adverse reactions as scalp dryness and irritation. In this paper we propose a novel approach for minoxidil sulphate (MXS) delivery based on a solid effervescent formulation. The aim was to investigate whether the particle mechanical movement triggered by effervescence would lead to higher follicle accumulation. Preformulation studies using thermal, spectroscopic and morphological analysis demonstrated the compatibility between effervescent salts and the drug. The effervescent formulation demonstrated a 2.7-fold increase on MXS accumulation into hair follicles casts compared to the MXS solution (22.0±9.7μg/cm2 versus 8.3±4.0μg/cm2) and a significant drug increase (around 4-fold) in remaining skin (97.1±29.2μg/cm2) compared to the drug solution (23.5±6.1μg/cm2). The effervescent formulations demonstrated a prominent increase of drug permeation highly dependent on the effervescent mixture concentration in the formulation, confirming the hypothesis of effervescent reaction favoring drug penetration. Clinically, therapy effectiveness could be improved, increasing the administration interval, hence, patient compliance. More studies to investigate the follicular targeting potential and safety of new formulations are needed.