Content Uniformity Of Tablets Research Articles

A Review: Novel Granulation Technology

All the pharmaceutical Active pharmaceutical Ingredients (API) and Pharmaceutical excipients will have different particle size. While formulating a dosage form, particles from raw materials will tend to separate from other due to their rheological properties. There could be a condition where fine particles separate from the larger particles causing demixing or uneven distribution of active with its excipients leading to tablet content uniformity issue. To overcome this problem, particle enlargement or particle cohesiveness with or without additional aid is necessary, which could be achieved by granulation. Hence granulation technology is important in the formulation of pharmaceutical oral solid dosage form. Granulation is the process of adhering fine particles agglomerate into a large particle using two most common methods i.e. wet granulation and dry granulation/compaction. Day by day technological innovation is happening in all fields and pharmaceutical granulation process is also not an exemption. The objective of present review is to focus the novel granulation technology and how it is differing from the conventional granulation technology.

Manufacturing process transfer to a 30 kg/h continuous direct compression line with real-time composition monitoring

Transferring an existing marketed pharmaceutical product from batch to continuous manufacturing (CM) without changes in regulatory registration is a challenging task in the pharmaceutical industry. Continuous manufacturing can provide an increased production rate and better equipment utilisation while retaining key quality attributes of the final product. Continuous manufacturing necessitates the monitoring of critical quality attributes in real time by appropriate process analytical tools such as near infra-red (NIR) probes. The present work reports a successful transfer of an existing drug product from batch to continuous manufacturing process without changing the formulation. A key step was continuous powder blending, whose design and operating parameters including weir type, agitation rate, dynamic hold-up and residence time were systematically investigated with respect to process repeatability. A NIR-based multivariate data model for in-line composition monitoring has been developed and validated against an existing quality control method for measuring tablet content uniformity. A continuous manufacturing long-run with a throughput of 30 kg/h (approx. 128,000 tablets per hour), uninterrupted for 320 min, has been performed to test and validate the multivariate data model as well as the batch to continuous process transfer. The final disintegration and dissolution properties of tablets manufactured by the continuous process were found to be equivalent to those manufactured by the original batch process.

Improving fluorescence emission of cyproheptadine by hindering its intramolecular photoinduced electron transfer (PET): Application to content uniformity testing and human plasma

The ability to determine antihistaminic drugs in biological matrices is critical for the medication adherence assessment. Among these antihistaminic medications, cyproheptadine (CPD); that is acting as a potent first-generation antihistaminic drug that has been extensively prescribed for allergic patients. Most of the established approaches for CPD detection are not appropriate for this purpose owing to their weak sensitivity, lack of rapidity, and complicated experimental procedures. Herein, we present a very fast, highly sensitive, and reproducible approach for the detection of CPD in its pure form, tablet formulation, and spiked human plasma. The photoluminescence approach depends on hindering the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom present on the piperidine ring of CPD by making the surrounding medium acidic using 1.0 M acetic acid. Based on blocking PET, the target CPD drug has been sensitively detected from 5.0 to 500 ng mL−1 with a very low detection and quantitation limit of 7.01 and 21.25 ng mL−1, respectively. Moreover, the established approach was used for checking the tablet content uniformity testing for each tablet and spiked human plasma, and noteworthy, the matrices interference was insignificant.

UV/Vis spectroscopy as an in-line monitoring tool for tablet content uniformity

Continuous manufacturing provides advantages compared to batch manufacturing and is increasingly gaining importance in the pharmaceutical industry. In particular, the implementation of tablet processes in continuous plants is an important part of current research. For this, in-line real-time monitoring of product quality through process analytical technology (PAT) tools is crucial. This study focuses on an in-line UV/Vis spectroscopy method for monitoring the active pharmaceutical ingredient (API) content in tablets. UV/Vis spectroscopy is particularly advantageous here, because it allows univariate data analysis without complex data processing. Experiments were conducted on a rotary tablet press. The tablets consisted of 7– 13 wt% theophylline monohydrate as API, lactose monohydrate and magnesium stearate. Two tablet production rates were investigated, 7200 and 20000 tablets per hour. The UV/Vis probe was mounted at the ejection position and measurements were taken on the tablet sidewall. Validation was according to ICH Q2 with respect to specificity, linearity, precision, accuracy and range. The specificity for this formulation was proven and linearity was sufficient with coefficients of determination of 0.9891 for the low throughput and 0.9936 for the high throughput. Repeatability and intermediate precision were investigated. Both were sufficient, indicated by coefficients of variations with a maximum of 6.46% and 6.34%, respectively. The accuracy was evaluated by mean percent recovery. This showed a higher accuracy at 20000 tablets per hour than 7200 tablets per hour. However, both throughputs demonstrate sufficient accuracy. Finally, UV/Vis spectroscopy is a promising alternative to the common NIR and Raman Spectroscopy.

The application of Near-Infrared Spatially Resolved Spectroscopy in scope of achieving continuous real-time quality monitoring and control of tablets with challenging dimensions

In scope of achieving real-time release of tablets, quality attributes need to be monitored and controlled through Process Analytical Technology tools such as near-infrared spectroscopy (NIRS). The authors evaluated the suitability of NIR-Spatially Resolved Spectroscopy (NIR-SRS) for continuous real-time monitoring and control of content uniformity, hardness and homogeneity of tablets with challenging dimensions. A novel user-friendly research and development inspection unit was used as standalone equipment for the analysis of small oblong tablets with deep-cut break lines. A total of 66 tablets varying in hardness and Active Pharmaceutical Ingredient (API) content were inspected, with each tablet being analysed five times and measurements repeated on three different days. Partial Least Squares (PLS) models were developed to assess content uniformity and hardness, of which the former showed higher accuracy. The authors attempted to visualize tablet homogeneity through NIR-SRS spectra by regressing all spectra obtained during a single measurement using a content uniformity PLS model. The NIR-SRS probe demonstrated its potential towards real-time release testing through its ability to quickly monitor content uniformity, hardness and visualize homogeneity, even for tablets with challenging dimensions.

Utility of dansyl chloride for the establishment of a sensitive spectrofluorimetric approach for estimating midodrine hydrochloride: application to content uniformity testing.

A new, straightforward spectrofluorimetric approach with high sensitivity was established for determining midodrine hydrochloride based on derivatizing this drug through its reaction with 5-(dimethylamino)naphthalene-1-sulfonyl chloride (dansyl chloride). The highly fluorescent product was extracted with methylene chloride, and then its emission was measured at 532 nm after excitation at 339 nm. The reaction was conducted in aqueous medium containing 0.1 M borate buffer (pH 8.2). The results showed that the proposed method is sensitive with high linearity in the range from 0.1 to 3 μg mL-1. The lower limits of detection and quantitation were 29 and 88 ng mL-1, respectively. Furthermore, the proposed approach was analytically assessed by applying the ICH guidelines. The suggested approach was effectively utilized for the estimation of the medicine in its marketable tablet formulations with excellent recovery and without any interfering effect from excipients. Moreover, the presented approach was utilized to test the content uniformity of commercial tablets following the USP guidelines.

Practices of tablet splitting and dose uniformity of fragments at public hospitals in Ethiopia: A cross-sectional study supported by experimental findings.

To assess the practices and dose uniformity of tablet splitting at selected public hospitals in Northwest Ethiopia. A hybrid study method was employed to see the overall practices of tablet splitting. A prospective cross-sectional study was conducted to explore the practices of tablet splitting by administering structured questionnaires to patients and pharmacy professionals. Experimental data on dose and content uniformity of split tablets were obtained from the results of drugs split by study subjects. The content uniformity assay was performed using UV/Vis spectrophotometry. A total of 241 patients and 82 pharmacy professionals participated in the cross-sectional study. The majority of patient participants (51.3%) faced problems while splitting their tablet medications and this had a significant association with the education level of the patients (χ2 = 60.5; p = 0.001). Enteric-coated formulations were dispensed to be split, despite the precaution given by the manufacturers against splitting or crushing these products. Splitting of enteric-coated products accounts for 11% of the total drugs that were dispensed to be taken after a split. The mean of weight variation test for the half tablets does not meet the specifications set in pharmacopoeias when splitting was done by patients. The unscored haloperidol tablets were hard to split and resulted in a significant weight variation of half-tablets than the scored furosemide tablets. Moreover, the weight of 4 out of 20 fragments that were split by patients deviated at least by 15%. This finding showed that the tablet-splitting practices are poor and do not meet the specifications set by pharmacopoeias. Splitting by patients resulted in significantly higher dose variation and weight loss of fragments than splitting by pharmacists.

Green Chemistry Method Based on Native Fluorescence for Estimation of Recently Approved Anti-neoplastic Drug Sotorasib

A new, simple, green and highly sensitive method has been established for quantification of recently approved antineoplastic drug Sotorasib (SOTO) in its bulk, tablets and biological fluids. The method depends on measuring the intrinsic fluorescence of the studied drug at wavelengths 350/410 nm at the optimal conditions. Validation of this method was performed following the guidelines of ICH. The proposed method shows linearity over a range of concentration 0.1-1.0 µg mL-1 with detection and quantification limits of 0.028 and 0.89 µg mL-1 respectively. Due to its high sensitivity, the suggested method was applied for quantification of the cited drug in spiked plasma and urine. The suggested strategy was also applied to evaluate the content uniformity in commercial tablets following the USP guidelines.

Using of eosin Y as a facile fluorescence probe in alogliptin estimation: Application to tablet dosage forms and content uniformity testing

New simple sensitive and reliable spectrofluorimetric approach was established for the determination of the antidiabetic drug; Alogliptin (ALG) in its pure and tablet forms. The developed approach is depended on the suppressive action of ALG on the eosin Y native fluorescence. The quenching action of ALG on the eosin Y native fluorescence was measured at acidic medium pH: 3.5, emission wavelength 541 nm (λex. 260 nm). The relative fluorescence intensity (RFI) was measured, and it was directly proportional to ALG concentration in the concentration range of (15–110) μg/mL. The developed and optimized approach was entirely validated regarding to ICH guidelines. The developed method application was successfully extended for ALG content uniformity test (CU). The distribution fraction (DF), rate constants (K), and free energy changes (ΔG°) were calculated. The results obtained were compared to that of the published spectrophotometric one.

Varied Bulk Powder Properties of Micro-Sized API within Size Specifications as a Result of Particle Engineering Methods.

Micronized particles are commonly used to improve the content uniformity (CU), dissolution performance, and bioavailability of active pharmaceutical ingredients (API). Different particle engineering routes have been developed to prepare micron-sized API in a specific size range to deliver desirable biopharmaceutical performance. However, such API particles still risk varying bulk powder properties critical to successful manufacturing of quality drug products due to different particle shapes, size distribution, and surface energetics, arising from the anisotropy of API crystals. In this work, we systematically investigated key bulk properties of 10 different batches of Odanacatib prepared through either jet milling or fast precipitation, all of which meet the particle size specification established to ensure equivalent biopharmaceutical performance. However, they exhibited significantly different powder properties, solid-state properties, dissolution, and tablet CU. Among the 10 batches, a directly precipitated sample exhibited overall best performance, considering tabletability, dissolution, and CU. This work highlights the measurable impact of processing route on API properties and the importance of selecting a suitable processing route for preparing fine particles with optimal properties and performance.

Prediction of tablet weight variability from bulk flow properties by sparse modeling

Die filling is a critical step in the pharmaceutical tableting process as it determines the uniformity in tablet weight, which affects the drug content uniformity and appearance of tablets. With the progress in powder flow characterization, a wide variety of bulk flow properties can be obtained, and several studies have been conducted to predict tablet weight variability (TWV) from bulk flow properties by applying multivariate analysis; however, there is still room for improvement in the selection of properties for predictive model construction. In this study, least absolute shrinkage and selection operator regression, a type of sparse modeling, was applied to select the critical flow properties from various ones, and TWV was predicted. To obtain blends with a wide range of properties, 27 powder blends were prepared by changing the active pharmaceutical ingredients (APIs), API loading in the formulation, and the grade of the lubricant. Bulk flow properties were evaluated, and a good prediction model was obtained by selecting five out of 14 bulk flow properties. The constructed model also predicted TWV well in the validation dataset. The applied approach is useful for constructing a simple model to better understand the phenomenon (die filling in this case), and the constructed model can be expanded further by including blends manufactured by dry or wet granulation.

Design-of-experiment approach to quantify the effect of nano-sized silica on tableting properties of microcrystalline cellulose to facilitate direct compression tableting of binary blend containing a low-dose drug

There are challenges to implementing high-speed direct compression tableting for poor flow, low-density cohesive powder. Thus, excipients with adequate flowability and bulk density are desired to facilitate this process. As a major novelty, the effect of nano-sized silica (Aerosil 200®) on the extent of flow and packing properties enhancement was evaluated. A 32 full-factorial design was applied to investigate the influence of silica load (X1; 0.5–5%) and mixing time (X2; 1–10 min) as independent variables on flow, bulk density and compaction properties of microcrystalline cellulose (MCC). Optimized MCC-silica blend was subsequently used in tableting of Albuterol Sulphate as a model low-dose drug. Regression analysis demonstrated significant (p ≤ 0.05) effect of X1 and X2 on tableting properties of MCC with pronounced effect of X1. Besides, nano-sized silica exhibited a significant improve in flowability, bulk density and compaction properties of MCC. However, at higher silica loading (over 2.75%) a reduction in flow and compaction was observed. The superior performance of MCC was achieved at silica load of (2.40%) and mixing time of (9.66 min). Moreover, the optimized blend could be directly compressed into tablets with excellent content uniformity, adequate mechanical strength, fast disintegration (63 ± 0.64 s) and dissolution (>90% after 5 min) that leads to rapid response. Ultimately, dry coating of poor flow-low density powder using nano-sized silica is a promising approach to improve the content uniformity of low-dose tablets prepared by high speed direct compression tableting.

Assessment of the Quality of Diclofenac Tablets Marketed in Gombe Metropolis, Nigeria

Background: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) that inhibits the enzyme cyclo-oxygenase and decreases the synthesis of prostaglandins. Diclofenac tablet is one of the commonly used NSAID marketed in Gombe metropolis. Objectives: The study is aimed at assessing the quality of different brands of diclofenac tablets (50 mg) sold at Pharmacies and Patent medicine shops (PMS). Method: Ten diclofenac tablet brands were obtained from registered Pharmacy shops and labelled “A to J” while ten brands from PMS were labelled “K to T”. The quality of the tablets was evaluated using official and non-official parameters such as uniformity of weight; thickness; diameter; crushing strength (CS); friability (FR); disintegration time (DT), wetting time, dissolution testing and tablet content uniformity. Results: Brands A, E, J from Pharmacies and K, N, Q, R from PMS had mean CS within the range of 4-7 kgF. Others had CS > 7 kgF. The FR values of all the brands except F and T were <1.0 %. All the tablet brands except Q disintegrated in <15 min. All the brands obtained from pharmacies and PMS released >75 % of the drug within 30 min except brands G and T. Conclusion: Almost all the brands were of good quality because they passed the prescribed tests. But only a few tablet brands most especially G and T that showed slightly dissimilar results when compared with the BP specifications.

Spherical Agglomerates of Lactose Reduce Segregation in Powder Blends and Improve Uniformity of Tablet Content at High Drug Loads.

We report here on improved uniformity of blends of micronised active pharmaceutical ingredients (APIs) using addition of spherical agglomerates of lactose and enhanced blend flow to improve tablet content uniformity with higher API loads. Micromeritic properties and intra-particle porosity (using nano-computed X-ray tomography) of recently introduced spherical agglomerates of lactose and two standard lactose grades for the direct compression processes were compared. Powder blends of the individual lactose types and different micronised API drug loads were prepared and subjected to specific conditions that can induce API segregation. Tablet content uniformity during direct compression was related to the lactose material attributes. The distinctive micromeritic properties of the lactose types showed that spherical agglomerates of lactose had high intra-particle porosity and increased specific surface area. The stability of binary blends after intense sieving was governed by the intra-particle porosity and surface roughness of the lactose particles, which determined the retention of the model substance. Greater intra-particle porosity, powder specific surface area, and particle size of the spherical agglomerates provided greater adhesion of micronised particles, compared to granulated and spray-dried lactose. Thus the spherical agglomerates provided enhanced final blend flow and uniformity of tablet content at higher drug loads.

Determination and understanding of lead-lag between in-line NIR tablet press feed frame and off-line NIR tablet measurements

The influence of different tableting process parameters on lead-lag was studied by collecting in-line near-infrared (NIR) spectra in the filling chamber of the tablet press feed frame and off-line NIR tablet data. Lead-lag is defined as the difference in time and API concentration between the measured in-line feed frame NIR response and the off-line NIR tablet data. Lead-lag results from the product formulation blend undergoing additional mixing after passing the NIR probe inside the feed frame, before being filled into the dies of the tablet press. A design of experiments (DoE) was performed to evaluate the effect of the tableting process factors paddle speed, turret speed, overfill level, paddle speed ratio and feed frame type upon lead-lag. Paddle speed and turret speed were identified as the only tableting parameters affecting lead-lag. Lead-lag decreased with increasing paddle speed or turret speed and became negligible at high paddle speed and high turret speed. Overfill level, paddle speed ratio and feed frame type did not affect lead-lag, suggesting that the amount and the trajectory of the recirculating powder in the feed frame did not significantly vary and hence influence the lead-lag within the examined process factor ranges. Finally, a methodology was developed using the in-line feed frame NIR measurements for the continuous monitoring and control of blend potency and tablet content uniformity. Tablet diversion should start when the in-line feed frame monitored blend potency exceeds the predefined control limits and can discontinue when this blend potency is again within the control limits for a duration equal to the lead-lag time. A combination of continuous blend potency monitoring inside the feed frame and in-process tablet weight control allows real-time tablet content uniformity assurance. Although the findings of this study are restricted to the specific equipment, tableting parameter ranges and product formulation used, the suggested approach for lead-lag determination and continuous tablet content uniformity monitoring can be applied to any rotary tablet press and product formulation.

Evaluation of Transmission Raman spectroscopy and NIR Hyperspectral Imaging for the assessment of content uniformity in solid oral dosage forms✰

Purpose: The objective of the present study was to explore and compare fast and non-destructive Transmission Raman Spectroscopy (TRS) and Near Infrared Hyperspectral imaging (NIR HSI) for the development of predictive quantitative methods to determine content uniformity (CU) of tablets. Methods: A set of single Active Pharmaceutical Ingredients (API) tablets with nine concentration levels of caffeine ranging from 12.75%w/w to 17.75%w/w and another set of double API tablets with five concentration levels of model API A* (5.25%w/w - 9.25%w/w) and caffeine (7%w/w – 13%w/w) were prepared. Chemometric prediction models were developed using partial least square (PLS 1) and later tested using a test set for both single and double API tablets. ResultsCalibration PLS1 models were developed for both single and double APIs using a combination of S-G 1st derivative and SNV data pre-processing steps that offer an optimal model performance with the lowest cross-validation error and bias. The root mean square error of prediction (RMSEP) for the PLS1 model for single API caffeine tablets using TRS and NIR HSI was 0.27% and 0.36% respectively. The RMSEP for the PLS1 models built using TRS for the double API tablets was 0.29% for API A and 0.34% for caffeine. Similarly, for the NIR HIS prediction models the RMSEP was 0.43% for API A and 0.56% for caffeine. ConclusionOverall TRS presented a 25–30% more accurate prediction capability compared to NIR HSI in this specific sample sets. Nevertheless, both TRS ad NIR HSI possess the potential to be employed as rapid, nondestructive techniques to replace classical wet- chemistry methods for at- or off-line determination of tablet CU.

Experimental and computational evaluation of kolliphor RH 40 as a new fluorescence enhancer in development of a micellar-based spectrofluorimetric method for determination of lapatinib in tablets and urine.

This study describes, for the first time, the experimental and computational investigations for evaluation of kolliphor RH 40 as a fluorescence enhancer surfactant in development of a spectrofluorimetric method for determination of lapatinib (LAP), a tyrosine kinase-inhibitor drug approved for targeted therapy of breast cancer. The investigations involved the ability of kolliphor RH 40 to form micelles with LAP and its enhancing effect on the weak native fluorescence of LAP at 420 nm after its excitation at 292 nm. Different variables were experimentally investigated: types of organized media, diluting solvent, buffer type and its pH value. The optimum values of the most influencing variables on the interaction of kolliphor RH 40 with LAP were refined by the computational response surface methodology (RSM). Under the optimized conditions, it was found that kolliphor RH 40 forms micelles with LAP, and its fluorescence enhancing ability was higher than other surfactants tested by ~ 10-folds. This micellar-enhanced effect of kolliphor RH 40 was employed in the development of a new sensitive spectrofluorimetric method for the accurate determination of LAP. The method was validated according to the guidelines of the International Conference on Harmonization (ICH) for validation of analytical procedures. The relative fluorescence intensity (RFI) was in excellent linear relationship (correlation coefficient was 0.998) with the LAP concentrations in the range of 50–1000 ng/mL. The method limit of detection (LOD) was 27.31 ng/mL and its accuracy was ≥ 99.82%. The method was successfully applied to the determination of LAP in its pharmaceutical tablets, tablets dissolution testing and content uniformity. The method application was extended to the determination of LAP in urine samples with an accuracy of 99.82 ± 3.45%. The method is considered as an eco-friendly green approach and more efficient alternative method to the existing analytical methodologies for determination of LAP.

Development and Evaluation of Feline Tailored Amlodipine Besylate Mini-Tablets Using L-lysine as a Candidate Flavouring Agent.

Felines may find orally administered medicines unpalatable, thus presenting a problem in the treatment of chronic conditions such as hypertension, a commonly diagnosed condition in felines requiring daily administration of medication. A pertinent example is amlodipine besylate, formulations of which are known to be poorly tolerated by cats. There is therefore a need to develop feline-specific delivery approaches that are both simple to administer and mask the taste of the drug, thereby enhancing the owner’s commitment to treatment and the associated therapeutic outcome for the companion animal. In addition, it is helpful to develop accessible and reproducible means of assessing taste for pre-clinical selection, hence the use of recently developed taste biosensor systems for veterinary applications is an area of interest. This study focuses on developing feline-specific amlodipine besylate formulations by improving the taste using a suitable flavouring agent while reducing dosage form size to a 2 mm diameter mini-tablet. The choice of l-lysine as a flavouring agent was based on the dietary and taste preference of cats. The impact of l-lysine on the taste perception of the formulation was evaluated using a biosensor system (E-tongue) fitted with sensors sensitive to bitter tastes. The results showed l-lysine successfully masked bitterness, while the drug release studies suggest that it has no impact on drug dissolution. In addition, tableting parameters such as tablet mass uniformity, content uniformity, tablet diameter, thickness and hardness were all satisfactory. The present study suggests that amlodipine besylate mini-tablets containing l-lysine could improve the palatability and in turn support product acceptability and ease of administration. These data could have an impact on orally administered medicines for cats and other veterinary species through product differentiation and competitive advantage in the companion animal market sector. The study also outlines the use of the electronic tongue as a tool for formulation selection in the veterinary field.

Rapid Determination of Acarbose in Tablets by 1H NMR Spectroscopy

Introduction: Acarbose, an anti-diabetic drug, is commonly used to treat diabetes mellitus type 2. Determinationof acarbose is crucial for routine quality control of acarbose tablets. Materials and Methods: In this report, a rapid, stable and precise method was developed and validated for the quantification of acarbose in tablets by 1H NMR. Two characteristic signals at 5.80 and 2.31 ppm were used to determine acarbose. The assay was linear over a concentration range of 0.25-10.0 mg/mL. The precision was 0.26% and 1.02% for signals at 5.80 and 2.31 ppm, respectively. The average recoveries of acarbose were 99.7% and 99.2%, with RSD values 0.51% and 0.61% at two signals, respectively. Results and Discussion: The content of tested tablets was 100.4% and 100.8% of the label claim with RSD values 0.96% and 1.47% at two signals, which met the requirement of Chinese Pharmacopoeia criteria for content uniformity of tablets. The assay has been successfully applied to determine the content of acarbose in tablets for quality evaluation. Conclusion: This method has been successfully applied to determine the content of acarbose in tablets for quality evaluation.

Calcitriol tablets with hybrid lipid-based solid dispersions with enhanced stability and content uniformity

Calcitriol, as the biologically active form of vitamin D3, is essential for patients with renal osteopathy. The solubilization, stabilization, and content uniformity are key issues in its formulation development. In our previous study, the incomplete release of calcitriol was solved by using the hybrid lipid-based solid dispersion (SD) for calcitriol. However, good stability and content uniformity are still urgently needed. In this study, solid lipid with antioxidant properties and liquid lipid compatible with calcitriol were employed as hybrid lipid carrier (HLC) to establish a solid dispersion. Moreover, the content uniformity of tablets with hybrid lipid carrier based SDs (HLCTs) was further guaranteed due to the multi-dispersion of calcitriol in HLC, solidification, and blank granules. Additionally, the compression of the blank granules was adjusted by the water content. The mixing method of calcitriol-containing and blank granules was also optimized. The obtained HLCTs were evaluated for hardness, disintegration time, in vitro drug dissolution, content uniformity, and stability. Satisfactory HLCTs were developed successfully in this study with superior content uniformity and better stability than the commercial soft capsule (Rocaltrol®). It was proved to be a promising formulation for drugs with poor water-solubility, instability to oxygen and heat, and dose-related toxicity.