Direct Compression Tablets Research Articles

Direct compression tablet formulation of trimetazidine through systematic screening of oxalate salts.

Salt formation has been extensively used to modulate and improve the properties of active pharmaceutical ingredients (API), such as solubility, stability and mechanical properties. Tablets of the anti-angina drug, trimetazidine (TMZ) are currently manufactured using the wet granulation process, rather than the more cost-effective direct compression method. In an effort to address the two main challenges associated with the commercial dihydrochloride salt (TMZ-2HCl), i.e., poor flowability and high hygroscopicity, we have screened and prepared three new oxalate (Oxa) salts of TMZ, i.e., TMZ:Oxa 1:1 (mono-salt), 2:1 (hemi-salt) and 1:2 (di-salt). All of the three salts exhibited improved solid-state properties over TMZ-2HCl, including flow, tabletability, and stability against high humidity. Among the three salts, the TMZ-Oxa (1:2) di-salt demonstrates overall superior properties, establishing it as the most promising alternative crystal form. Consequently, using the di-salt, we developed a direct compression tablet formulation that shows potential for commercial manufacturing.

Study of MCC, Mannitol and SiO2 Based Co-processed Excipient for Improving the Direct Compression Properties of Paracetamol using SeDeM/SeDeM-ODT Expert System

Co-processed excipients have enhanced functionality attributes required for developing tablet dosage forms by direct compression technology. In the present study, mannitol, microcrystalline cellulose, and silicon dioxide were developed by dry granulation and proposed as a viable solution for correcting the flowability and compressibility issues commonly encountered in developing paracetamol tablets. SeDeM (12 parameter based) and SeDeM ODT (15 parameter based) expert systems were employed as tools for developing orally disintegrating tablets of paracetamol. SeDeM diagram of paracetamol, mannitol, microcrystalline cellulose and co-processed excipients were prepared and parametric index values of 3.9 and 2.01 indicated poor flowability and compressibility properties of paracetamol. The percentage of corrective excipient required to correct the flowability and compressibility of paracetamol was then calculated followed by preparation of SeDeM ODT expert system diagrams. An increase in concentration of silicon dioxide from 1% to 5% in the co-processed excipient resulted in a decrease in dissolution rate due to increased apparent viscosity/ gel-like structure at higher concentrations of silicon dioxide. The study revealed that co-processed excipient sample with 2.5% of silicon dioxide showed the highest IGCB value of 6.39, implying its suitability for the direct compression of tablets.

Applying the SeDeM Expert Diagram System for Characterization of Multiple Component Powder Mixtures for Fixed-dose Combination Matrix-type Tablet Formulations

Background: The SeDeM Expert Diagram System (SeDeM EDS) is an innovative formulation tool that provides an index of compressibility, which can be used to predict a pow-der’s suitability for direct compression to produce acceptable tablets. Objective: This study investigated the application of this tool to evaluate multiple component powder formulation mixtures for direct compression of tablets. The SeDeM EDS was specifically used to characterize powder mixtures for fixed-dose combination (FDC) matrix-type tablets that contained multiple active ingredients, which has not been done previously with SeDeM EDS. Methods: The FDC matrix-type tablets contained diclofenac sodium and vitamins B1, B6 and B12 in fixed ratios, intended for the management of peripheral neuropathy. The parameters of the SeDeM EDS were determined for the multiple-component powder mixtures and the indices were calculated to predict direct compressibility. The FDC tablets were subsequently manufactured uti-lizing direct compression and subjected to pharmacotechnical test evaluations to measure the ac-curacy of the SeDeM EDS’s predictions. Results: This study proved the versatility of the SeDeM EDS and its utility to adequately charac-terize FDC powder mixtures for matrix-type tablets manufactured by direct compression. Addi-tionally, a new calculation was suggested to determine the percentage of corrective excipients re-quired in the case when multiple incidence factor values are below the value of 5. Prediction of the correct quantity of corrective excipient to be added is important to obtain an acceptable direct compressible formulation. Conclusion: The results obtained confirmed that the SeDeM EDS correctly predicted the performance of all formulations.

MICROCRYSTALLINE CELLULOSE: A BIOPOLYMER WITH DIVERSIFORM APPLICATIONS

With characteristics, such as white color, tasteless, odorless, neutral, non-reactive, non-toxic, stable, biocompatible, and biodegradable, along with excellent compaction properties, high mechanical strength, and low density, microcrystalline cellulose (MCC) stands out as a top excipient for direct compression tablets. As the demand for renewable, eco-friendly, and non-fossil materials becomes increasingly imperative, this most abundant biopolymer on Earth is sought not only in the pharmaceutical industry, but also in the cosmetics, food, construction, and wastewater treatment sectors. This review paper highlights the importance of this substance by describing its various applications across the mentioned industrial sectors, with a focus on direct compression tablets as the most commonly used oral dosage form. Results from numerous experiments have demonstrated the benefits of MCC as a component in a variety of products, including direct compression tablets, coated spheres, topical preparations, ice cream, cocoa, fried beef patties, sausages, cement, foamed concrete, and adsorbents for heavy metals in wastewater treatment.

Facilitating direct compaction tableting of fine cohesive APIs using dry coated fine excipients: Effect of the excipient size and amount of coated silica

The possibility of attaining direct compression (DC) tableting using silica coated fine particle sized excipients was examined for high drug loaded (DL) binary blends of APIs. Three APIs, very-cohesive micronized acetaminophen (mAPAP, 7 μm), cohesive acetaminophen (cAPAP, 23 μm), and easy-flowing ibuprofen (IBU, 53 μm), were selected. High DL (60 wt%) binary blends were prepared with different fine-milled MCC-based excipients (ranging 20- 37 μm) with or without A200 silica coating during milling. The blend flowability (flow function coefficient −FFC) and bulk density (BD) of the blends for all three APIs were significantly improved by 1 wt% A200 dry coated MCCs; reaching FFC of 4.28 from 2.14, 7.82 from 2.96, and > 10 from 5.57, for mAPAP, cAPAP, and IBU blends, respectively, compared to the uncoated MCC blends. No negative impact was observed on the tablet tensile strength (TS) by using dry coated MCCs despite lower surface energy of silica. Instead, the desired tablet TS levels were reached or exceeded, even above that for the blends with uncoated milled MCCs. The novelty here is that milled and silica coated fine MCCs could promote DC tableting for cAPAP and IBU blends at 60 wt% DL through adequate flowability and tensile strength, without having to dry coat the APIs. The effect of the silica amount was investigated, indicating lesser had a positive impact on TS, whereas the higher amount had a positive impact on flowability. Thus, the finer excipient size and silica amounts may be adjusted to potentially attain blend DC processability for high DL blends of fine APIs.

Characterization of Acid Hydrolyzed Taro Boloso-I (Colocasia esculenta Cultivar) Starch as a Diluent in Direct Compression of Tablets.

Corn, wheat, rice, potato, and cassava starches have been widely used as pharmaceutical excipients. However, the search for cost-effective local starch alternatives is necessary due to the availability and usage constraints. In Ethiopia, various plant species, including Taro Boloso-I, have been explored as potential sources of pharmaceutical starch. It is a variety of Colocasia esculenta with a high tuber yield and high starch content. However, the native starch requires modifications to enhance its functionality. Therefore, this study aimed to improve the native starch through acid modification and evaluate its performance as a direct compressible tablet excipient. The native starch was treated with a 6% w/v HCl solution for 192 hours, resulting in acid-modified Taro Boloso-I starch, which was then evaluated for suitability for direct compression. XRD patterns of both the native and modified starch showed characteristic A-type crystals, with significantly higher relative crystallinity observed in the latter. Additionally, the acid-modified starch exhibited a lower moisture content and improved flow properties. The compaction study also demonstrated its improved compactibility (tensile strength: 16.82 kg/cm2), surpassing both the native starch (13.17) and Starch 1500® (11.2). The modified starch also showed a lower lubricant sensitivity compared to the native starch and Starch 1500®. Furthermore, paracetamol tablets made with the modified starch exhibited higher mechanical strength and lower friability in all paracetamol concentrations. It incorporated up to 40% paracetamol while maintaining acceptable tablet characteristics, whereas the native starch and Starch 1500® were limited to 30% (w/w). Based on these findings, the modified starch showed promise as an alternative direct compressible excipient in tablet manufacturing.

Impact of Methods of Preparation on Mechanical Properties, Dissolution Behavior, and Tableting Characteristics of Ibuprofen-Loaded Amorphous Solid Dispersions.

This study aims to improve the biopharmaceutical, mechanical, and tableting properties of a poorly soluble drug, ibuprofen (IBP), by preparing amorphous solid dispersion (ASD) followed by a sustained-release tablet formulation. A suitable polymer to develop an ASD system was chosen by utilizing the apparent solubility of IBP in various polymer solutions. ASDs containing various ratios of IBP and selected polymer were prepared by the melt fusion (MF) method. ASD containing optimized drug-polymer ratio prepared by freeze-drying (FD) method was characterized and compared physicochemically. The solubility of IBP in water increased 28-fold and 35-fold when formulated as ASD by MF and FD, respectively. Precise formulations showed amorphization of IBP and increased surface area, improving solubility. The dissolution pattern of optimized ASD-IBP in pH 6.8 phosphate buffer after 60 min in MF and FD was enhanced 3-fold. In addition, direct compression tablets comprising optimized ASD granules from MF and FD were made and assessed using compendial and noncompendial methods. ASD-IBP/MF and ASD-IBP/FD formulations showed a similar drug release profile. In addition, 12 h of sustained IBP release from the ASD-IBP-containing tablets was obtained in a phosphate buffer with a pH of 6.8. From the dissolution kinetics analysis, the Weibull model fitted well. The drug release pattern indicated minimal variations between tablets formed using ASD-IBP prepared by both procedures; however, pre- and postcompression assessment parameters differed. From these findings, the application of ASD and sustained-release polymers in matrix formation might be beneficial in improving the solubility and absorption of poorly soluble drugs such as IBP.

Transdermal Delivery of Pramipexole Using Microneedle Technology for the Potential Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disease primarily impacting neurons responsible for dopamine production within the brain. Pramipexole (PRA) is a dopamine agonist that is currently available in tablet form. However, individuals with PD commonly encounter difficulties with swallowing and gastrointestinal motility, making oral formulations less preferable. Microneedle (MN) patches represent innovative transdermal drug delivery devices capable of enhancing skin permeability through the creation of microconduits on the surface of the skin. MNs effectively reduce the barrier function of skin and facilitate the permeation of drugs. The work described here focuses on the development of polymeric MN systems designed to enhance the transdermal delivery of PRA. PRA was formulated into both dissolving MNs (DMNs) and directly compressed tablets (DCTs) to be used in conjunction with hydrogel-forming MNs (HFMNs). In vivo investigations using a Sprague-Dawley rat model examined, for the first time, if it was beneficial to prolong the application of DMNs and HFMNs beyond 24 h. Half of the patches in the MN cohorts were left in place for 24 h, whereas the other half remained in place for 5 days. Throughout the entire 5 day study, PRA plasma levels were monitored for all cohorts. This study confirmed the successful delivery of PRA from DMNs (Cmax = 511.00 ± 277.24 ng/mL, Tmax = 4 h) and HFMNs (Cmax = 328.30 ± 98.04 ng/mL, Tmax = 24 h). Notably, both types of MNs achieved sustained PRA plasma levels over a 5 day period. In contrast, following oral administration, PRA remained detectable in plasma for only 48 h, achieving a Cmax of 159.32 ± 113.43 ng/mL at 2 h. The HFMN that remained in place for 5 days demonstrated the most promising performance among all investigated formulations. Although in the early stages of development, the findings reported here offer a hopeful alternative to orally administered PRA. The sustained plasma profile observed here has the potential to reduce the frequency of PRA administration, potentially enhancing patient compliance and ultimately improving their quality of life. This work provides substantial evidence advocating the development of polymeric MN-mediated drug delivery systems to include sustained plasma levels of hydrophilic pharmaceuticals.

Trace polymer coated clarithromycin spherulites: Formation mechanism, improvement in pharmaceutical properties and development of high-drug-loading direct compression tablets

Clarithromycin (CLA) is a high dose antibiotic drug exhibiting poor flowability and tabletability, making the tablet development challenging. This study aims to develop spherulitic CLA by introducing trace amount of polymer in crystallization solution. Its formation mechanism, physicochemical properties and potential for the direct compression (DC) tablets development were also investigated. Morphological analyses and the in situ observation on crystallization process revealed that the CLA spherulites are formed by fractal branching growth from both sides of the threadlike precursor fibers. 1H NMR analysis and nucleation time monitoring indicated that the existence of hydroxypropyl cellulose in solution slowed down the crystal nucleation and growth rate by forming hydrogen bonding interactions with CLA molecules, making the system maintain high supersaturation, providing high driving forces for CLA spherulitic growth. In comparison to commercial CLA, the CLA spherulites exhibit profoundly improved flowability, tabletability and dissolution behaviors. XPS, contact angle and Raman mapping analysis confirmed the presence of a thin HPC layer on the surfaces and interior of CLA spherulitic particles, resulting in increasing powder plasticity, interparticulate bonding strength and powder wettability, thus better tabletability and dissolution performances. The improved flowability and tabletability of CLA spherulites also enabled the successful development of DC tablet formulation with a high CLA loading (82.8 wt%) and similar dissolution profiles to reference listed drug. This study provides a novel solid form of CLA with superior manufacturability for further development.

Sample Size Requirements of a Pharmaceutical Material Library: A Case in Predicting Direct Compression Tablet Tensile Strength by Latent Variable Modeling.

The material library is an emerging, new data-driven approach for developing pharmaceutical process models. How many materials or samples should be involved in a particular application scenario is unclear, and the impact of sample size on process modeling is worth discussing. In this work, the direct compression process was taken as the research object, and the effects of different sample sizes of material libraries on partial least squares (PLS) modeling in the prediction of tablet tensile strength were investigated. A primary material library comprising 45 materials was built. Then, material subsets containing 5 × i (i = 1, 2, 3, …, 8) materials were sampled from the primary material library. Each subset underwent sampling 1000 times to analyze variations in model fitting performance. Both hierarchical sampling and random sampling were employed and compared, with hierarchical sampling implemented with the help of the tabletability classification index d. For each subset, modeling data were organized, incorporating 18 physical properties and tableting pressure as the independent variables and tablet tensile strength as the dependent variable. A series of chemometric indicators was used to assess model performance and find important materials for model training. It was found that the minimum R2 and RMSE values reached their maximum, and the corresponding values were kept almost unchanged when the sample sizes varied from 20 to 45. When the sample size was smaller than 15, the hierarchical sampling method was more reliable in avoiding low-quality few-shot PLS models than the random sampling method. Two important materials were identified as useful for building an initial material library. Overall, this work demonstrated that as the number of materials increased, the model's reliability improved. It also highlighted the potential for effective few-shot modeling on a small material library by controlling its information richness.

Development of direct compression Acetazolamide tablet with improved bioavailability in healthy human volunteers enabled by cocrystallization with p-Aminobenzoic acid

Pharmaceutical cocrystallization has been widely used to improve physicochemical properties of APIs. However, developing cocrystal formulation with proven clinical success remains scarce. Successful translation of a cocrystal to suitable dosage forms requires simultaneously improvement of several deficient physicochemical properties over the parent API, without deteriorating other properties critical for successful product development. In the present work, we report the successful development of a direct compression tablet product of acetazolamide (ACZ), using a 1:1 cocrystal of acetazolamide with p-aminobenzoic acid (ACZ-PABA). The ACZ-PABA tablet exhibits superior biopharmaceutical performance against the commercial tablet, DIAMOX® (250 mg), in healthy human volunteers, leading to more than 50 % reduction in the required dose.

From waste to a resource? Hemicelluloses enhance the dissolution and stability of the amorphous state of carbamazepine

Both synthetic and natural polymers are used as excipients in various pharmaceutical preparations. Natural polymers offer advantages, such as abundant availability, cost-effectiveness, non-toxicity, biocompatibility, and biodegradability. Hemicelluloses are highly promising natural polymers for pharmaceutical applications due to their advantageous colloidal properties, but their ability to solubilize poorly water-soluble drugs and stabilize their amorphous form is currently virtually unexplored. In this study, we showed the applicability of birch, spruce and wheat straw hemicelluloses as tablet excipients and their ability to enhance dissolution and stability of a model drug, carbamazepine (CBZ), in amorphous solid dispersions. The hemicelluloses formed sufficiently strong tablets by direct-compression, although addition of CBZ weakened the tablets. The hemicelluloses did not modify drug release from the tablets when compared to plain CBZ powder. Solid dispersions with CBZ were identified as amorphous one-phase mixtures, with hydrogen bonding between the hemicelluloses and CBZ. The mixtures remained stable for at least nine months under 40 °C/23 % RH. Dissolution of the amorphous solid dispersions decreased with increasing hemicellulose molar mass. Up to 7.6-fold CBZ supersaturation was achieved, although it did not improve CBZ permeation through a PAMPA (parallel artificial membrane permeability assay) barrier when compared to the corresponding physical mixtures. In summary, birch, spruce, and wheat straw hemicelluloses formed direct-compressed tablets and stable amorphous solid dispersions that may improve dissolution properties of drugs. Differences exist between hemicelluloses from different plant sources and thus more research with structurally different drug substances is needed in the future.

The Development of Oral Solid Dosage Forms Using the Direct-Compression Tableting of Spray-Dried Bacteriophages Suitable for Targeted Delivery and Controlled Release

This study addresses the challenge of developing a cheap, patient-friendly alternative to antibiotics using bacteriophages for gastrointestinal applications. It explores the feasibility of manufacturing an enteric solid dosage form containing a salmonella-specific Myoviridae phage, Felix O1, encapsulated in spray-dried trehalose/Eudragit microparticles. The spray-dried powder was further formulated by combining the spray-dried microparticles with magnesium stearate to facilitate the fabrication of tablets using direct compression. The paper presents a comprehensive evaluation of the tablets with measurements of phage viability during tablet fabrication using a range of compression settings and, after tablet disintegration, dissolution and friability. Phage viability measurements were performed using storage stability testing of spray-dried powders and tablets in sealed vials at 4 °C, 20 °C and 30 °C and under different humidity conditions of 0%, 50% and 65% RH. The recommended compression force range was found to be 10–15 kN for a standard 10 mm diameter tablet. The storage of tablets at 4 °C/0% RH was found to be the most favourable condition resulting in a ~1 log loss in titre over a six-month storage period. Storage at higher temperatures and samples exposed to high levels of humidity resulted in a significant loss in phage viability. The paper highlights challenges in developing phage formulations suitable for direct-compression tableting, which afford the phages protection when exposed to temperatures and humidity levels that do not require a cold supply chain.

Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica.

Designing a robust direct compression (DC) formulation for an active pharmaceutical ingredient (API) with poor flow and compaction properties at a high API load is challenging. This study tackled two challenges: the unfavorable flow characteristics and tableting problems associated with a high-drug-loading canagliflozin (CNG), facilitating high-speed DC tableting. This was accomplished through a single-step dry coating process using hydrophilic nano-sized colloidal silica. A 32 full-factorial experimental design was carried out to optimize the independent process variables, namely, the weight percent of silica nanoparticles (X1) and mixing time (X2). Flow, bulk density, and compaction properties of CNG-silica blends were investigated, and the optimized blend was subsequently compressed into tablets using the DC technique. A regression analysis exhibited a significant (p ≤ 0.05) influence of both X1 and X2 on the characteristics of CNG with a predominant effect of X1. Additionally, robust tablets were produced from the processed powders in comparison with those from the control batch. Furthermore, the produced tablets showed significantly lower tablet ejection forces than those from the control batch, highlighting the lubrication impact of the silica nanoparticles. Interestingly, these tablets displayed improved disintegration time and dissolution rates. In conclusion, a dry coating process using silica nanoparticles presents a chance to address the poor flow and tableting problems of CNG, while minimizing the need for excessive excipients, which is crucial for the effective development of a small-sized tablet and the achievement of a cost-effective manufacturing process.

Comparative Direct Compression Property of a Novel Pregelatinized Starch in Paracetamol Tablets.

Among all the pharmaceutical dosage forms, tablets are still the most preferred and the most commonly used option because of their advantages. The direct compression method of tablet preparation exempts several steps needed in the granulation method. Therefore, the pursuit of better direct compression tablet excipients is evident in contemporary research endeavors. Pregelatinized Taro Boloso-I starch has comparable flow properties and higher compressibility and compactibility than Starch 1500®. However, there is no evidence in the literature regarding the lubricant sensitivity and dilution potential of pregelatinized Taro Boloso-I starch. This study was aimed at performing the in vitro evaluation of paracetamol tablets prepared using pregelatinized Taro Boloso-I starch as a direct compression excipient using paracetamol as a model drug. Taro Boloso-I starch was pregelatinized, and its properties including amylose to amylopectin ratio, densities, flow properties, swelling power, water solubility index, particle morphology, moisture content, and moisture sorption profile were evaluated. Furthermore, the lubricant sensitivity test, dilution potential study, and compatibility test with the paracetamol drug using ATR spectroscopy were performed. The properties of the directly compressed tablets prepared accordingly were evaluated. The majority of evaluations were performed in comparison with Starch 1500®. Results and Discussion. PGTBIS had a significantly lower amount of amylose than Starch 1500®. In the ATR-IR spectra of the mixture of the paracetamol and pregelatinized PGTBIS, all the major absorbance peaks of the drug were maintained indicating the absence of chemical modifications. PGTBIS showed better flow properties than Starch 1500®. The modified starch was shown to withstand magnesium stearate up to 0.5% concentration. PGTBIS could accommodate higher drug cargo than Starch 1500® with acceptable tablet properties. Accordingly, PGTBIS starch could be taken as a potential direct compression excipient.

Eutectic phase transition during tablet manufacture: effect of melting point of eutectic forming drug

The aim was to investigate eutectic transition during tableting and storage. Mixtures of lidocaine and series of NSAIDs with increasing melting point were used as model systems to guide formulators to scaleup eutectic forming materials gaining enhanced dissolution while avoiding deleterious physical changes. Physical mixtures of NSAIDs with lidocaine were prepared at eutectic forming ratio. These were directly compressed, dry co-ground before compression, or compressed after wet granulation. Dissolution of tablets was compared to corresponding dry co-ground mixture. Thermograms of direct compressed tablet were compared to co-ground mixture and pure compound. Stability of direct compressed tablets was assessed. Tableting initiated eutexia which enhanced dissolution of NSAIDs. Eutexia was associated with tablet softening in case of low melting point ketoprofen and aceclofenac. Wet granulation hastened eutexia developing unacceptable tablet in case ketoprofen and aceclofenac. Tablets prepared by direct compression of physical mixtures underwent gradual eutectic transition upon storage with the magnitude of eutectic transition reducing with increased melting point of NSAIDs. Ketoprofen was physically unstable but aceclofenac degraded chemically as well. Tenoxicam and meloxicam tablets were physically and chemically stable. Direct compression after physical mixing is the best tableting technique, but low melting point drugs should consider different strategy before compression.

Application of co-precipitated glutinous rice starch as a multifunctional excipient in direct compression tablets

Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which limits its use in direct compression tablets. This study aimed to create a multifunctional direct compression excipient (filler binder disintegrant) with improved flowability from GRS by the co-precipitation method. The physicochemical and pharmaceutical properties of the co-precipitated GRS (cpGRS) were investigated. The optimum conditions for producing cpGRS (0.43 M sodium hydroxide solution, 7.09% PVP K30, 14.02% calcium carbonate, 95 min of mixing time and pH of 6.97) resulted in 68.80% yield, fair to good flowability, acceptable tablet strength, and fast disintegration. The FT-IR spectra of cpGRS showed no significant shifts in the key peaks, which indicates that there was an absence of chemical interactions within cpGRS. X-ray diffractograms also showed no significant changes, indicating that the GRS granules, calcium carbonate, and PVP K30 components remained unaltered during co-precipitation. cpGRS also demonstrated a dilution capacity of 50% when paracetamol was used as model drug. When cpGRS was combined with domperidone or propranolol hydrochloride it showed a better deformation capability than the physical mixtures. Although cpGRS was sensitive to lubricant, the hardness and tensile strength were higher than common strength for general purpose use in tablets. When compared to the physical mixture, pregelatinized starch and directly compressible calcium carbonate, the results showed that cpGRS tablets of both model drugs passed the friability test, demonstrated the best disintegration property, provided the fastest and highest drug release profile for propranolol, and improved the drug release profile for domperidone. For propranolol-cpGRS tablets, dissolution medium at different pH did not affect the dissolution profile. For domperidone-cpGRS tablets, the pH of dissolution medium did affect the dissolution profile of the tablets. This was according to the API solubility. These results reveal that cpGRS is an excellent multifunctional i.e., filler, binder, and disintegrant excipient suitable for direct compression tablets. The main component is natural. The preparation method is simple, quick, and efficient. This method does not produce harmful waste and requires only basic equipment, and affordable reactants and devices.

Preparation and in vitro/in vivo characterization of sustained-release ciprofloxacin-carrageenan complex

The goal of the study was to look into drug-polyelectrolyte complexation between ciprofloxacin (Cipro) and λ-carrageenan (CRG), and to employ the complex as a sustained-release matrix. The maximum binding capacity of the complexation was determined using the dialysis bag method and employed to prepare the complex. In comparison to Cipro, CRG, and their physical mixing, the complex was examined using differential scanning calorimetry, Fourier infrared spectroscopy, powder X-ray diffraction, and scanning electron microscopy. Cipro-CRG matrices, manufactured as direct compression tablets based on the greatest binding capacity, were assessed for swelling, erosion and drug release in 0.1 M HCl, in comparison with those of CRG, Hydroxypropyl methylcellulose (HPMC) and Cipro-HPMC matrices. In vivo absorption study comparing the Cipro-CRG matrix to Cipro immediate-release tablet was also carried out.The greatest binding capacity of Cipro to CRG was 55% (w/w). Multiple interactions, including electrostatic interaction, Vander wall forces, and hydrogen bonding, have been proposed to be involved in complexation with drug amorphization. As a result of the complexation, the swelling and erosion properties of CRG changed, with Cipro-CRG matrix showing substantially less swelling and erosion than Cipro-free CRG matrix. Cipro-CRG matrix exhibited swelling and erosion similar to Cipro-HPMC matrix. However, the former matrix demonstrated Cipro release with significantly less burst impact and a significantly slower release rate. Furthermore, Cipro-CRG matrices in vivo demonstrated slow-prolonged oral drug absorption with consequent significant changes in pharmacokinetic parameters in comparison to those obtained for immediate-release tablets.

Comparative Evaluation of the Powder and Tableting Properties of Regular and Direct Compression Hypromellose from Different Vendors.

Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting). These differences can affect their physicomechanical properties, and so this study aims to characterise the particle size and mechanical properties of HPMC K100M polymer grades from four different vendors. Eight polymers (CR and DC grades) were analysed using scanning electron microscopy (SEM) and light microscopy automated image analysis particle characterisation to examine the powder's particle morphology and particle size distribution. Bulk density, tapped density, and true density of the materials were also analysed. Flow was determined using a shear cell tester. Flat-faced polymer compacts were made at five different compression forces and the mechanical properties of the compacts were evaluated to give an indication of the powder's capacity to form a tablet with desirable strength under specific pressures. The results indicated that the CR grades of the polymers displayed a smaller particle size and better mechanical properties compared to the DC grade HPMC K100M polymers. The DC grades, however, had better flow properties than their CR counterparts. The results also suggested some similarities and differences between some of the polymers from the different vendors despite the similarity in substitution level, reminding the user that care and consideration should be given when substitution is required.

Combination of synthetic and natural polymers on the characteristics and evaluation of transdermal hydrogel-forming microneedles preparations integrated with direct compressed tablets reservoir sildenafil citrate

Erectile dysfunction (ED) is a disorder of the male reproductive organs due to the inability to achieve penile erection. Hydrogel-forming microneedles (HFMs) integrated with direct compression tablets (DCT) reservoir SC was developed. HFMs were produced utilizing polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), and chitosan as a combination of a mixture of synthetic and natural polymers as well as glutaraldehyde as a crosslinking agent. The swelling study of hydrogel film for all formulas had a swelling percentage profile >900%. Characterization for all HFMs formulas possessed a good profile with a percentage reduction in height of MNs <10% and was considered capable of penetrating the dermis layer. Ex vivo permeation studies on HFMs with DCT reservoir SC showed that the largest amount of SC drug permeated at 24 h was 3384.7 ± 90.81 μg/cm2. This study has succeeded in presenting the development of a transdermal preparation of HFMs integrated with DCT reservoir SC.