Wet Granulation Research Articles

Antimicrobial and acaricide sanitizer tablets produced by wet granulation of spray-dried soap and clove oil-loaded microemulsion.

A novel sanitizer tablet containing clove essential oil (CO) microemulsion was developed. A preformulation study using nuclear magnetic resonance and thermal analyses showed component compatibility. The main components of the samples remained intact despite a color change, probably due to a strong acid-base interaction between eugenol and diethanolamine. The CO microemulsion showed acaricidal and larvicidal activities superior to the commercial product, with product efficacy of 99.9% and larvae mortality of 94%. Optimal spray-drying conditions were achieved with inlet and outlet temperatures of 50°C and 40°C, respectively, an aspiration rate of 1 m3 min⁻1, and a 0.25 L h⁻1 injection flow. The feed suspension comprised 50% (v/v) liquid soap, 37.5% (v/v) water, 12.5% (v/v) ethanol, and 5.0% (w/v) silica. This formulation and processing parameters allowed for successful free-flow powder formation, providing a suitable matrix for incorporating the CO microemulsion via wet granulation without heating. Finally, sanitizer tablets produced from such granules resulted in a uniform product with low weight variation (coefficient of variation of 0.15%), eugenol content of 95.5% ± 3.3, and friability of 0.58%. Furthermore, the tablets showed rapid aqueous dispersion, forming a colloidal system with particle sizes of 221 nm and a zeta potential of -17.2 mV. Antimicrobial activity tests demonstrated the effectiveness of the sanitizer tablet against bacteria and fungi, exhibiting comparable antimicrobial potency to isolated CO. Hence, the sanitizer tablet developed represents a promising candidate as a practical and efficient solution for pest control, offering strong antimicrobial and acaricidal activity.

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

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

Corrigendum to “Evaluation of binders in twin-screw wet granulation – Optimization of tabletability” [Int. J. Pharm. 659 (2024) 124290

Corrigendum to “Evaluation of binders in twin-screw wet granulation – Optimization of tabletability” [Int. J. Pharm. 659 (2024) 124290

Characterization and evaluation of okra gum as a tablet binder

The type and amount of binders decisively influence the characteristics of tablets prepared by wet granulation procedure. Commonly used binders like acacia, gelatin, starch and hydrolyzed starch have natural origin. The aim of this study was to evaluate the effectiveness of a new binder extracted from Hibiscus esculentus (Okra gum) in tableting. Okra gum was extracted from the pods of Okra fruit by maceration in distilled water followed by filtration of viscous solution as well as precipitation of gum extract by using acetone. To evaluate the binder effectiveness, two models, including a placebo formulation (lactose) and a drug formulation (Acetaminophen, Ibuprofen, and/or Calcium acetate) were evaluated. Granules were prepared by different concentrations (0.5-6 %w/w) of Okra gum and tableted using a Kilian single punch press. Cornstarch (12.5 % w/w) and P.V.P (22 %w/w) were employed as the standard binders for comparison. The physical properties of the granulates and those of the tablets including disintegration time and dissolution rate were studied. The properties of granulates (bulk and tapped density, granule strength, flowability) as well as those of tablets (hardness, friability, disintegration time) were generally good. Moreover, the physical properties of Ibuprofen and Calcium acetate tablets containing Okra gum showed sufficient hardness, desirable disintegration time and low friability. The percent of drug released after 45 minutes were 15 %, 44 % and 96 % for Acetaminophen, Ibuprofen and Calcium acetate tablets, respectively. Okra gum produces some tablet formulations with good hardness and friability. However, this binder prolongs the dissolution rate of some slightly soluble drugs and hence may be good candidate for sustained release formulations. (Symecko C., Rhodes C, et.al.,1995)

Development and Characterization of Fast-Dissolving Tablets to Enhance Bioavailability of BCS Class II Drugs by Solid Dispersion Method

Background: Rapid tablet or capsule dissolution requires the tablet to disintegrate and dissolve at a higher rate, enhancing drug dissolution and bioavailability. Suitable disintegrants have shown an appreciable rate of disintegration or dissolution. Using factorial design for formulation to improve bioavailability is a key focus in pharmaceutical research to enhance dissolution Methods: Azelnidipine (Azp) tablets were formulated with Hydroxypropyl β-cyclodextrin (HβCD), β-cyclodextrin (βCD), and Kolliphor HS15 (HS15) to enhance solubility. A 23 factorial design optimized the formulation, focusing on disintegration time (DT) and time for 90% dissolution (T90). Eight formulations (F1-F8) were prepared using the kneading method. Tablets were evaluated for physical properties, drug content, friability, dissolution, and drugexcipient interactions (FTIR and DSC). The optimal formulation (F9) was determined via desirability analysis. Results: Tablets showed acceptable Carr's index (CI), Hausner ratio (HR), and Angle of Repose (AR). Increasing βCD concentration decreased DT, enhancing water absorption and faster dissolution. βCD tablets had the lowest DT among the formulations, with F4 showing the best disintegration. Higher HS15 concentration also reduced DT, with F8 achieving the highest drug release (T90%) within 60 minutes. R² values ranged from 0.922 to 0.994, indicating high predictability. The optimal formulation had a desirability of 1.0, consisting of 3.523 mg HS15, 28.4 mg βCD, and 1.49 mg βCD, with a DT of 102 ± 1.13 seconds and 98% dissolution. FTIR and DSC confirmed no drug–excipient interactions. Conclusion: Optimized super disintegrant concentrations and wet granulation techniques resulted in tablets with strong mechanical properties, rapid disintegration, and consistent drug content. Future research and in vivo studies should explore additional excipient combinations.

Understanding of Wetting Mechanism Toward the Sticky Powder and Machine Learning in Predicting Granule Size Distribution Under High Shear Wet Granulation.

The granulation of traditional Chinese medicine (TCM) has attracted widespread attention, there is limited research on the high shear wet granulation (HSWG) and wetting mechanisms of sticky TCM powders, which profoundly impact the granule size distribution (GSD). Here we investigate the wetting mechanism of binders and the influence of various parameters on the GSD of HSWG and establish a GSD prediction model. Permeability and contact angle experiments combined with molecular dynamics (MD) simulations were used to explore the wetting mechanism of hydroalcoholic solutions with TCM powder. Machine learning (ML) was employed to build a GSD prediction model, feature importance explained the influence of features on the predictive performance of the model, and correlation analysis was used to assess the influence of various parameters on GSD. The results show that water increases powder viscosity, forming high-viscosity aggregates, while ethanol primarily acted as a wetting agent. The contact angle of water on the powder bed was the largest and decreased with an increase in ethanol concentration. Extreme Gradient Boosting (XGBoost) outperformed other models in overall prediction accuracy in GSD prediction, the binder had the greatest impact on the predictions and GSD, adjusting the amount and concentration of adhesive can control the adhesion and growth of granules while the impeller speed had the least influence on granulation. The study elucidates the wetting mechanism and provides a GSD prediction model, along with the impact of material properties, formulation, and process parameters obtained, aiding the intelligent manufacturing and formulation development of TMC.

Effects of zirconium diboride addition on porosity reduction in laser metal deposition of tungsten carbide–cobalt cermet material

Laser metal deposition of tungsten carbide–cobalt (WC-Co) cermet material is a promising means of improving the wear resistance of metal products. However, laser metal deposition of WC-Co has constraints on its practical use because a clad bead of WC-Co often includes numerous gas pores. Earlier studies have found CO gas generation in a molten pool by reaction of carbon and oxygen to be the main cause of gas porosity in a WC-Co clad bead. Preventing the gas reaction is important to obtain clad beads with few pores. The addition of elements with strong affinity for oxygen, such as aluminum, was found to be effective for porosity reduction in a clad bead. However, the addition of highly reactive pure aluminum particles on WC-Co powder presents some difficulties for industrial use. For this study, zirconium diboride (ZrB2), a chemically stable compound, was used as an additive to WC-Co powder. After WC-Co powder with adhered ZrB2 particles was prepared using a wet granulation process, laser metal deposition was conducted. Zirconium stemming from the dissolution of ZrB2 in the molten pool was found to have the effect of trapping oxygen elements as solid zirconium oxides. Consequently, gas generation in the molten pool by the reaction of carbon and oxygen was restrained. Clad beads having few pores and fine microstructures were obtained. Observations of the molten pool behavior taken using a high-speed camera indicated that ZrB2 addition drastically improves process stability compared to processes using conventional WC-Co powder.

Coating Tablets, Compositions, Recent Advancement and Current Status: A Comprehensive Review

Conventional Tablets are solid oral dosage forms that contain an active pharmaceutical ingredient (API) along with excipients. These tablets are typically prepared through direct compression, wet granulation, or dry granulation. They are designed to disintegrate and release the API in a controlled or immediate manner, depending on the formulation. Tablet coating is a vital process in pharmaceutical technology, designed to improve the therapeutic efficacy, patient compliance, and stability of oral dosage forms. This comprehensive review explores the key aspects of tablet coating, including the types, compositions, and recent advancements. Coating materials such as polymers, plasticizers, and pigments are discussed in detail, along with their roles in controlling drug release, masking taste, and enhancing aesthetic appeal. The recent advancements focus on innovative coating techniques like film coatings, enteric coatings, and the application of nanotechnology to improve precision and functionality. Additionally, the current status of tablet coating is analyzed in terms of regulatory compliance and industry trends. The review highlights the future potential of personalized coatings, smart coatings, and environmentally friendly approaches, showcasing the evolving landscape of tablet coating technologies/pans in modern pharmaceutical manufacturing and development. Keywords: Table coating; dosage form; enteric; coating pans; formulation; advancement; polymers

Surfactant-Assisted Wet Granulation-Based Matrix Tablets without Exceptional Additives: Prolonging Systemic Exposure of Model BCS Class II Ketoprofen.

The present studywas aimed to ameliorate the issue of solubility and thereby, bioavailability of ketoprofen, a BCS Class II drug. The sustained release matrix tablets (MT) were prepared using surfactant-assisted wet granulation (SAWG) with 1-5% of different surfactants. The tablet characteristics were within the compendial limits. The selected sustained release-compliant matrix tablet formulation containing granules prepared using 3% Soluplus® (MT2) released the drug by swelling-erosion. In human volunteers, MT2 attained the maximum plasma concentration (Cmax) of 5.72µg /ml ± 0.30 h, time to Cmax (Tmax) of 5.56 ± 0.30 h and maintained the plasma concentration above its minimum effective concentration (MEC), 0.7 µg.ml-1 till 24h. A control formulation, prepared from granules without surfactant (MT16), promptly attained Cmax of 9.62 ± 0.76 µg/ml within 1h but rapidly declined to below MEC in 8h. Area under the curve from initial point to infinity (AUC0-∞) of MT2 (78.65 ± 7.64 µg.h.ml-1) was 2.29 folds higher than 34.39 ± 3.06 µg.h.ml-1 of MT16. With decreased Cmax, increased AUC0-∞, delayed Tmax and retained ketoprofen concentration above MEC for longer time, MT2 corresponded with the in-vitro sustained drug release characteristic. There is a likelihood of administration of once-a-day single dose of MT2 without plasma fluctuations, expected from two doses of MT16. SAWG helped developing a swellable-erodible sustained release matrix tablet formulation of ketoprofen with the desired biopharmaceutical and pharmacokinetics properties, merely by addition of Soluplus® in granules and without incorporation of any special ingredients or the major manipulation of the formulative ingredients in the formulation.

Comparative study between the Full Factorial, Box–Behnken, and Central Composite Designs in the optimization of metronidazole immediate release tablet

The purpose of this paper is to summarize the fundamentals, benefits and limitations of various models of Design of Experiments (DoE) such as 2-Level Full Factorial Design, Central Composite Design (CCD), and Box–Behnken Design (BBD) while establishing a comparison between these models by taking the Metronidazole immediate release (IR) tablets as a case study. Metronidazole IR tablets were prepared by wet granulation method. The Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) were selected based on literature review and prior knowledge about the formulation. Critical Material Attributes (CMA) (concentration of binder, super disintegrant, and glidant), and Critical Process Parameters (CPP) (compression of the tablets) were identified based on their risk to the CQA. Screening and optimization of the CMA were performed using DoE. From the Full Factorial Design, it was observed that the disintegration time and dissolution at 30 min were significantly influenced by the selected CMAs. These significant factors were further optimized using CCD and BBD to achieve the constraints (minimum disintegration and maximum dissolution). The levels of povidone K30, crospovidone, and magnesium stearate were optimized to 10 mg, 32 mg, and 1.6 mg respectively using CCD and BBD.

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

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

Population balance modelling and reconstruction by quadrature method of moments for wet granulation

Population balance methods utilised in multiphase flow simulations mark a significant advancement in computational fluid dynamics. However, existing approaches exhibit shortcomings, such as being prone to inaccuracies or being computationally prohibitive. Addressing these challenges, a recent innovation in closure for the method of moments is the introduction of quadrature based moments methods (QBMM). Discretising a distribution by a number of discrete elements, QBMM facilitate efficient and accurate tracking of density distributions, particularly for particle size distributions (PSD). However, obtaining the full particle size distribution information using these methods requires reconstructing the distribution from a finite set of moments, which is not a trivial step.This study introduces a novel combination of the maximum entropy reconstruction (MER) and QBMM, establishing a robust and rapid framework for the time evolution and reconstruction of PSDs. As proof of concept for this framework, we focus on the direct quadrature method of moments (DQMOM) with spatially homogeneous and monovariate distributions. We show that coupling of MER with DQMOM has numerous advantages. To verify the framework, special cases of constant growth, aggregation, and breakage are considered for which analytical solutions can be found. Furthermore, we show the advantage of using DQMOM with volume-based over length-based distributions, and address numerical as well as theoretical issues.Application of the framework is successfully conducted on the evolution of the PSD from a twin-screw wet granulation dataset, considering all active primary physical mechanisms in a wet granulation process, namely growth, aggregation, and breakage. This showcases the consistency of the proposed framework and underscores its applicability to real-world scenarios.

Nitrosamine mitigation: NDMA impurity formation and its inhibition in metformin hydrochloride tablets

The mitigation of nitrosamine formation in drug products has been studied and approaches such as using formulations with pH modifiers and antioxidants have been shown to decrease the formation of nitrosamines. However, more studies are needed to explore the effectivness of mitigation strategies with different drug models and formulations. The primary objective of this work was to assess the role of different antioxidants and pH modifiers in tablet formulations to mitigate the formation of NDMA, prepared in-house, using metformin hydrochloride as a model drug. A study design for manufacturing metformin hydrochloride formulations was created to evaluate potential mitigation stratigies. The formulations were prepared by wet granulation that included a sodium nitrite spike and various antioxidants such as ascorbic acid, caffeic acid and ferulic acid at various concentrations that may inhibit nitrosamine formation. The study design also included pH modifiers such as hydrochloric acid and sodium carbonate. The metformin hydrochloride formulations were placed under stability conditions that included humidity, temperature and time over a six month period. NDMA inhibition was found to be most effective in formulations with basic pH, followed by the addition of tested antioxidants with 0.1% concentrations in the formulations. All tested antioxidants showed complete mitigation in formulations with 0.5% and 1% concentrations. In summary, basic pH and the inclusion of antioxidants exhibited the potential to mitigate the formation of NDMA in metformin hydrochloride tablets.

Characterization of extracted alpha cellulose from Manihot esculenta (cassava) peels as formulation aid for paracetamol tablet

Background: Alpha-cellulose as a pharmaceutical excipient can be employed as a binding agent in tablet formulation. Cassava peels husk are waste agricultural material and is being investigated for its α-cellulose for use in oral solid pharmaceutical formulation. Purpose: The objective of this study is to extract α-cellulose from cassava peels agro-industrial waste using a standard method, subject the extracted cassava peels cellulose and determine its phytochemical and physicochemical properties of formulated granules of paracetamol. Methods: Alpha-cellulose from cassava peel was extracted using alkali method. The fresh peels were prepared, milled into slurry and de-watered to obtain a coarse wet material, dried, milled and sieved to obtain very fine powdered particles. Phytochemical analysis and characterization of extracted α-cellulose powder were determined. Differential scanning calorimetry (DSC), scanning electron micrographs (SEM), and x-ray diffractogram (XRD) analysis of extracted cassava peel cellulose were done. Paracetamol granules was prepared by wet granulation using varying concentrations of the binders. Results: DSC and XRD results revealed a semi-crystalline material with amorphous and crystalline regions. while the SEM showed a lumpy structure and reticular shape. Pre-compression evaluations of the formulated batches of paracetamol granules showed that cassava peels cellulose (CPC) have similar flow properties with those of microcrystalline cellulose BP (MCC) and acacia BP (ACA) powders respectively. The granules have free flow properties with average angles of repose (CPC ≤ 27.60 MCC < 26.90 and ACA ≤ 25.60), compressibility index (CPC ≤ 25, MCC ≤ 23 and ACA ≤ 21.7%), Hausner’s ratio (CPC ≤ 1.32, MCC ≤ 1.31, and ACA ≤ 1.27) respectively. Conclusion: The extracted cassava peel α-cellulose was found ideal as pharmaceutical excipient binder in oral solid dosage forms.

Autoencoder-based inverse design and surrogate-based optimization of an integrated wet granulation manufacturing process

In pharmaceutical manufacturing, integrating model-based design and optimization can be beneficial for accelerating process development. This study explores the utilization of Machine Learning (ML) techniques as a surrogate model for the optimization of a three-unit wet-granulation based flowsheet model for solid dosage form manufacturing. First, a reduced representation of a wet granulation flowsheet model is developed, incorporating a granulation and milling process, along with a novel dissolution model that accounts for the effect of particle size, porosity, and microstructure on dissolution rate. Two optimization approaches are compared, including an autoencoder-based inverse design and a surrogate-based forward optimization. Both methods address the bi-objective problem of maximizing dissolution time and product yield by identifying the optimal granulation and mill process parameters. For this case study, both approaches were effective and incurred a similar computational cost, averaging under 4 s. However, the autoencoder approach offers an advantage through dimensionality reduction, a feature not available in surrogate-based optimization. Dimensional reduction is particularly beneficial for complex process designs with numerous inputs and outputs. The lower dimensional representation helps improve process understanding through enhanced visualization of the process design space and facilitates feasibility studies involving multiple constraints. The autoencoder-based inverse design introduced in this work showcases an implementation of AI and ML in pharmaceutical process development, demonstrating the potential to enhance process efficiency and product quality in complex manufacturing scenarios.

A Comprehensive Study on Pharmaceutical Mini Tablets and Pellets

Mini tablets provide several benefits, including being very simple to make, requiring fewer coating ingredients, and having a lot of formulation development freedom. Children and older people like little tablets because they are simpler to swallow. Reduced dosage frequency and improved localization of the drugs are the objectives of controlled drug delivery systems are impacted. Mini tablets provide improved homogeneity and reduce variability in drug release among subjects, increasing the consistency and predictability of treatment. Some scaled-down tablets are accessible, like bio-adhesive, pH-responsive, purgative, pediatric, and oral deteriorating mini tablets. If any kind or explicit clinical requirements, they are intended to meet the patient's necessities. Different strategies for delivering circles, like direct compaction, wet granulation, or dry granulation, are contingent upon the result's ideal properties. Coatings in little vials can be utilized for different purposes, like flavour coatings, dampness or light security, or coatings of altered synthetic substances. The determination of coatings relies upon similarity with the dynamic fixing and the ideal delivery rate. The current article comprehensively reviews the dosage, types, manufacturing and analysis methods, benefits and challenges of the mini tablets, and recent technological advances.

Examining particle size growth in twin screw granulation up to steady state with acoustic emissions

The transient evolution of granules was studied to learn new details about the underlying mechanism for continuous wet granulation in a twin-screw extruder. Sieving and a new inline PAT for particle size development was used to gain these insights. The onset for steady state was established based on observing a consistent PSD, which occurred at five times the mean residence time of the process, over a range of degrees of fill (DF; 12–30 %). The early stages of startup for granulation were captured by the inline PAT, showing different stages of granule growth for particle sizes ranging from 102 to 2230 μm. The analysis found that conveying elements have a stronger influence on granule growth at a low DF whereas the kneading zone had a stronger influence on granule growth at a higher DF. This study presents new details on this black-box process while highlighting the unique value of PAT to twin-screw granulation.

Water interaction with MCC powder exposed to wetting–drying cycles: Comparison of capillary imbibition techniques

We investigate how wetting-and-drying (WD) cycles change the properties of microcrystalline cellulose (MCC) powder (Avicel PH101), due to hornification, by performing the following experiments: (i) drop absorption in a slightly compressed powder bed, (ii) capillary imbibition in a packed powder column, and (iii) drop absorption into tablets obtained by direct compression. We use the MCC powder as received, as well as the powder obtained after one or more WD cycles. In each case, the powder is sieved and fractionated into two samples, with different particle size distribution. First, we perform drop absorption experiments using both water and silicone oil (Polydimethylsiloxane - PDMS) drops. We observe that WD cycles increase the absorption time for water, a particularly marked effect after the first cycle, for both particle size distributions. Comparing the absorption times of water and oil drops we obtain a parameter β that characterizes the water-MCC interaction in lieu of the contact angle, and accounts for both capillary and swelling phenomena. We observed that the main effect is produced after the first WD cycle exhibited by a large (more than 50%) reduction in the β value. Column imbibition experiments performed using water and PDMS show that, initially, water penetrates at a larger rate than PDMS. This initialing faster water uptake is more significant for larger particles and fewer WD cycles. A power law regime is obtained in each case with a ζ exponent. In particular, a Washburn-like imbibition regime with ζ=0.5 is recovered at long times for both liquids. In the last experimental technique, we study the absorption of water drops deposited on tablets obtained by direct compression of the full distribution of powder particle sizes. We observe that absorption time increases with increasing number of WD cycles of the MCC powder. This is quantified by the 30% reduction of the ζ exponent that models the penetration rate of the drop.In summary, we use three kinds of experiments that cover a wide range of characteristic time scales to quantify the effect of WD cycles on the interaction of water with a swelling powder like MCC. The importance of comparing responses under different timescales is that the swelling phenomenon modifies the properties of the material in time, while imbibition happens. It is shown by this study that in some cases, the phenomena can be decoupled (droplet absorption in porous media) while in other cases it cannot be (droplet on tablets and intermediate times in capillary rise). Finally, at long times in capillary rise, even when the swelling and imbibition effects are not decoupled, it is possible to estimate the permeability ratio, χ, and its dependence with the WD cycles when the results are used in combination with the ones from the droplet absorption on powder test. The permeability decreased about 8 times for no WD cycles, and it decreased much less (2 and 3 for small and large particles respectively) for one and two WD cycles. We were able to quantitative characterize the effects of water-MCC interaction and this is important in order to predict how some pharmaceutical processes, like wet granulation, will be affected.

Formulation Variables Influencing the Development of Ketoconazole Gastroretentive Drug Delivery System

Background: Ketoconazole (KZ) is categorized as class II according to the Biopharmaceutics Classification System (BSC) classification, which shows a strong pH-dependent solubility where its solubility is enhanced under an acidic medium (pH below 3). This strong pH dependence results in unpredictable absorption and a wide range of bioavailabilities. Objective: To prolong the gastric residence time of KZ’s tablet to enhance KZ’s solubility and hence its bioavailability for better therapeutic activity. Methods: To prepare mucoadhesive tablets, we use both direct and wet granulation methods. We employed various evaluation tests to assess the prepared tablets. These tests encompass a range of assessments, including weight variation, hardness, thickness, friability, disintegration test, swelling study, mucoadhesive strength study, and in vitro drug release studies. Results: The study found that polymer viscosity, as well as polymer concentration, have a significant effect on mucoadhesive strength and drug release, whereas diluent type has a non-significant influence on drug release. We selected Formula 7, which employs xanthan gum as a mucoadhesive polymer in a 1:1 drug polymer ratio, as the optimum formula because it provides an accepted physico-mechanical property and releases 87% of the drug over 8 hours. Conclusions: Gastric mucoadhesive tablets may be an effective method of delivering active ingredients, as they provide a favorable environment that enhances their dissolution by extending their duration in the stomach, thereby increasing their bioavailability.

Formulation and evaluation of extended-release floating tablets of labetalol hydrochloride 200 mg

The aim of present work is to formulate and evaluate extended-release floating tablets of Labetalol HCL to improve the bioavailability, Patient compliance and solubility on oral floating drug of Labetalol HCL. Labetalol HCL is mainly used in the treatment of hypertension, which is BCS Class Ⅰ drug i.e. Highly soluble and highly permeable. The tablets were prepared by wet granulation method by using different concentrations of HPMC polymer. The tablets were evaluated for Preformulation characteristics, Pre compression parameters and post compression parameters. In-vitro dissolution studies were performed for all prepared formulations by using dissolution test apparatus employing a paddle stirrer at 50 rpm and 37 ± 0.5°C, 0.1N HCL buffer was used as dissolution medium. Samples of 5ml each were withdrawn at different time intervals. Each sample withdrawn was replaced with an equal amount of fresh dissolution medium. Samples were diluted and assayed at 302 nm using Agilent UV Visible double beam spectrophotometer. The increased drug release is due to the presence of low concentration of HPMC K4 m. The drug release kinetics was calculated for all the formulations, among all the formulations F8 was taken as optimized formulation whose percentage drug release was found to be 96%. It indicates the release follows zero order and Hixon kinetics. Hence formulation F8 was Considered as the optimized batch and stability studies were conducted at 40oc±2oc/75±5%RH, Storage condition for 3 months and no change was observed.