Thermolabile Drugs Research Articles

Cold Emulsified Nanoemulsion: Enhancing Delivery and Stability of Thermolabile Acyclovir

Acyclovir is an acyclic purine nucleoside widely used as an antiviral agent with good topical efficacy. Acyclovir is a thermolabile drug, making it challenging to formulate a stable and effective emulsion via a conventional emulsification process. This study aims to develop, optimize, and characterize the nanoemulsion of thermolabile drug acyclovir, manufactured by adopting a cold emulsification process and compare the physicochemical properties and diffusion pattern with a leading marketed formulation. Diffusion studies were conducted using Franz diffusion cells. The optimized formulation was subjected to quantitative estimation of acyclovir, impurity profiling, viscosity, pH, vesicle size, shape, and polydispersibility index (PDI). In the current study, the particle size of the nanoemulsion varies from 66.25 to 244.40 nm, and the zeta potential revealed a high negative surface charge on the particles. Transmission electron microscopy images revealed spherical-shaped, non-aggregated, and discrete globules. The in-vitro diffusion study of acyclovir nanoemulsion showed enhanced penetration efficacy than the conventional emulsion. All these observations signified that the cold emulsification process for manufacturing nanoemulsion is appropriate for thermolabile and pH-sensitive drugs. The study demonstrates enhanced stability and efficacy of optimized acyclovir nanoemulsion through cold emulsification.

THEDES as a drug product intermediate for improved melt-extrusion processibility of thermally labile active ingredients

Hot melt extrusion (HME) is extensively employed in the pharmaceutical industry, but its utilization of heat raises concerns over drugs’ thermal stability. Strategies to improve stability and processibility of thermolabile materials via salt formation and co-crystals engineering are found in the literature. In this work, it was attempted to use therapeutic deep eutectic solvents (THEDES) as a mean to achieve improved drug thermal stability through the formation of a charge-assisted strong hydrogen boding network. Thermogravimetric studies on THEDES formed using a thermolabile drug, lidocaine, with different non-steroidal anti-inflammatory agents (NSAIDs) were employed to test this hypothesis. The resulted three THEDESs in this study were all tested to be more thermally stable than the corresponding parent compounds, confirming the stabilizing effect from the THEDES bonding network. This investigation reintroduces THEDES as a drug product intermediate with improved processibility for HME.  

Mechanically promoted lipid-based filaments via composition tuning for extrusion-based 3D-printing

Lipid excipients are favorable materials in pharmaceutical formulations owing to their natural, biodegradable, low-toxic and solubility/permeability enhancing properties. The application of these materials with advanced manufacturing platforms, particularly filament-based 3D-printing, is attractive for personalized manufacturing of thermolabile drugs. However, the filament’s weak mechanical properties limit their full potential. In this study, highly flexible filaments were extruded using PG6-C16P, a lipid-based excipient belonging to the group of polyglycerol esters of fatty acids (PGFAs), based on tuning the ratio between its major and minor composition fractions. Increasing the percentage of the minor fractions in the system was found to enhance the relevant mechanical filament properties by 50-fold, guaranteeing a flawless 3D-printability. Applying a novel liquid feeding approach further improved the mechanical filament properties at lower percentage of minor fractions, whilst circumventing the issues associated with the standard extrusion approach such as low throughput. Upon drug incorporation, the filaments retained high mechanical properties with a controlled drug release pattern. This work demonstrates PG6-C16 P as an advanced lipid-based material and a competitive printing excipient that can empower filament-based 3D-printing.

Blackout in Ukraine and challenges regarding the storage of immunobiological drugs

An undeclared war has been going on in Ukraine for more than one year. Defeated at the front, Russia resorted to massive shelling of energy facilities with the aim of leaving Ukrainians without electricity and heat during the winter. As reported, since October 10, the Russians have fired more than a thousand missiles and drones at Ukrainian energy facilities. The shelling on November 23, 2022 led to a system crash — a blackout occurred. For the first time in the history of Ukraine, all of the country’s nuclear power units were shut down. In conditions of lack of light and non-working refrigerating chambers, the storage conditions of thermolabile immunobiological drugs became a new test for the medical community and patients. As you know, immunobiological drugs, which are widely used in the treatment of various rheumatological diseases, require strict storage conditions in the temperature range from +2 to +8°С. Under blackout conditions, it is difficult for Ukrainian patients to maintain optimal storage conditions for these drugs. The analysis of the studies showed that the majority of patients do not comply with the requirements for the storage of thermolabile drugs, even with the constant presence of light and electricity. Experts indicate that more and more thermolabile drugs are becoming available, and in most cases, these medications are dispensed to ambulatory patients. More thermolabile drugs are becoming available, and in most cases, these medications are dispensed to ambulatory patients. However, there is no regulation once medications are dispensed to patients and little is known with regard to what happens during transport and home storage. Previous studies suggest that these drugs are improperly stored. Future studies should focus on clinical consequences and possible solutions. It is recommended for Ukrainians to follow the rules and conditions of storage of heat-labile medicinal products during blackouts/emergency and stabilization blackouts.

Processability of mesoporous materials in fused deposition modeling for drug delivery of a model thermolabile drug

The incorporation of drug-loaded mesoporous materials in dosage forms prepared with fused deposition modeling (FDM) has shown the potential to solve challenges relating to additive manufacturing techniques, such as the stability of poorly-soluble drugs in the amorphous state. However, the addition of these non-melting mesoporous materials significantly affects the mechanical properties of the filament used in FDM, which in turn affects the printability of the feedstock material. Therefore, in this study a full-factorial experimental design was utilized to investigate different processing parameters of the hot melt extrusion process, their effect on various mechanical properties and the potential correlation with the filaments' printability. The thermolabile, poorly-soluble drug ibuprofen was utilized as a model drug to assess the potential of two mesoporous materials, Mesoporous Magnesium Carbonate (MMC) and a silica-based material (MCM-41), to thermally protect the loaded drug. Factorial and principal components analysis displayed a correlation between non-printable MCM-41 filaments and their mechanical properties where printable filaments had a maximum stress >7.5 MPa and a Young's modulus >83 MPa. For MMC samples there was no clear correlation, which was in large part attributed to the filaments' inconsistencies and imperfections. Finally, both mesoporous materials displayed a thermal protective feature, as the decomposition due to the thermal degradation of a significant portion of the thermolabile drug was shifted to higher temperatures post-loading. This highlights the potential capability of such a system to be implemented for thermosensitive drugs in FDM applications.

A Review of Various Manufacturing Approaches for Developing Amorphous Solid Dispersions

In recent years amorphous solid dispersions (ASD) has gained a tremendous response for improving the solubility of poorly water-soluble drug substances. Despite the stability challenges, various ASD commercial products have been successfully launched into the market over the last two decades. Among various manufacturing approaches, hot melt extrusion (HME) and spray drying techniques have attracted industries attributing to their simple manufacturing processes. In addition, KinetisolÒ, a solvent-free approach, is also being most widely investigated for developing ASDs since the thermal exposure time of the formulations is significantly less compared with the hot melt extrusion process. KinetisolÒ can be employed for developing ASDs of thermolabile drug substances. Another solvent-based technique, electrospinning, is also employed for developing nanofibers-based ASD. However, much research is warranted for the electrospinning process before implementing it in commercial manufacturing. Various critical factors such as drug-polymer solubility, the solubility of the drug in the polymer, drug-polymer interactions, type of manufacturing process, and storage conditions need to be considered for developing a stable and robust ASD formulation. This review mainly focuses on the most advanced manufacturing technologies of ASDs, namely HME, spray drying, KinetisolÒ, and electrospinning, along with a note on the various critical factors that affect the stability of ASD formulations.
 Keywords: amorphous solid dispersions; hot melt extrusion; spray drying; KinetisolÒ; electrospinning

3D printing hybrid materials using fused deposition modelling for solid oral dosage forms.

3D printing in the pharmaceutical and healthcare settings is expanding rapidly, such as the rapid prototyping of orthotics, dental retainers, drug-loaded implants, and pharmaceutical solid oral dosage forms. Through 3D printing, we have the capability to precisely control dose, release kinetics, and several aesthetic features of dosage forms such as colour, shape, and texture. Additionally, polypills can be created with combinations of medications in one solid dosage form at completely customisable strengths that would be extremely difficult to obtain commercially. As the technology and formulations developed through 3D printing are expanding, the development of new hybrid materials to obtain superior formulations are also gaining momentum. In this review we collate data on the importance of developing hybrid formulations of polymers, drugs and excipients necessary to produce reliable and high-quality 3D printed dosage forms with a special emphasis on fused deposition modelling (FDM). FDM technology is one of the most widely used forms of 3D printing and has demonstrated compatibility with unique polymer-based hybrids to allow for enhanced drug delivery, protection of thermolabile drugs, modifiable release kinetics, and more. The data collated covers different categories of hybrids as well as the methods used to fabricate them, and their respective effects on the properties of 3D printed solid oral dosage forms. Therefore, this review will provide an overview of upcoming and emerging trends in pharmaceutical 3D printing formulation compositions.

3D Printing of Thermo-Sensitive Drugs.

Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations.

Effect of processing conditions and material attributes on the design space of lysozyme pellets prepared by extrusion/spheronization

The present work aimed to investigate the impact of the critical material attributes on the design space of the production of lysozyme pellets with suitable biological and physical properties for the subsequent coating process. The effect of two brands of both lysozyme and conformation stabilizing mannitol on the behavior of the composition in an extrusion/spheronization process was studied, while the experiments were designed according to 23 factorial design. The kneading of the mass was carried out in a high shear granulator equipped with a specially designed granulation chamber (Opulus Ltd, Hungary) constructed with seven built-in sensors for the measurement of temperature and relative humidity (RH). The special chamber is a novel tool for the identification of the critical points during processing a thermolabile drug by providing the online monitoring of critical environmental parameters and could be used to accurately determine the effect of critical process parameters and material attributes. The prepared samples were investigated for their biological and physical properties. It was found that the critical material attributes have a potential effect on the production process and product quality, and highly influence the size of the process design space. Therefore, the screening of the formulation materials is a key factor in macromolecular drug development.

Systematic assessment of the drugs cold chain in Brazil by pharmaceutical professionals

One of the challenges in pharmaceutical logistics is to ensure that thermolabile drugs reach the patient with quality. This prospective cross-sectional study aimed to analyze the current cold chain scenario in Brazil. A semi-structured electronic questionnaire was applied for data collection. The total sample was 1793 pharmacists (CI: 99.998%; ME: 5%; p: 0.00002). 74.1% of the pharmacists reported that transportation is the most critical stage; 97.2% stated that the chosen mode influences the quality of the products; 52.5% reported only having partial parameters (tools) for the assessment of quality and that thermolabile medications possibly arrive altered to the final consumer due to the cold chain (59.8%); 66.9% do not have specific training on thermolabile medicines and 50.9% did not receive the technical data sheets of the products through the registration holders; 20.7% reported not being able to analyze or perform any activity related to qualification and validation. The absence of markings in the manual records (50.6%), the non-validation of the equipment used for conservation (30.6%) and the incorrect storage of medicines at domestic refrigerators (45.5%), near food (35.8%), were also noted. The non-measurement of the temperature of the products received was affirmed by 56.7%, as well as the use of thermometers to measure parameters (45.3%); 58.7% of the establishments do not have thermal mapping and 55.3% of the professionals are unaware of the thermal durability of the packaging. Due potentially inadequate situation, there is urgency to implement tools that guarantee the quality of thermolabile drugs in all its logistical stages.

Thermolabile drug storage in an ambulatory setting

More thermolabile drugs are becoming available, and in most cases, these medications are dispensed to ambulatory patients. However, there is no regulation once medications are dispensed to patients and little is known with regard to what happens during transport and home storage. Previous studies suggest that these drugs are improperly stored. The present study was designed to determine the storage conditions of thermolabile drugs once they are dispensed to the patient in the Hospital Pharmacy Department. This is a prospective observational study to assess the temperature profile of 7 thermolabile drugs once they are dispensed to ambulatory patients at a tertiary care hospital. A data logger was added to the medication packaging. Temperature was considered inappropriate if one of the following circumstances were met: any temperature record less than or equal to 0 °C or over 25 °C; temperatures between 0–2 or 8–25 °C for a continuous period over 30 min. The time series of temperature measurements obtained from each data logger were analyzed as statistically independent variables. The data shown did not undergo any statistical treatment and must be considered directly related to thermal measurements. One hundred and fourteen patients were included and 107 patients were available for the analysis. On the whole, a mean of 50.6 days (SD 18.3) were measured and the mean temperature was 6.88 °C (SD 2.93). Three data loggers (2.8%) maintained all the measurements between 2 and 8 °C with less than 3 continuous data (< 30 min) out of this range but no data over 25 °C or below or equal to 0 °C. 28 (26.2%) data loggers had at least one measurement below zero, 1 data logger had a measurement greater than 25 °C and 75 (70.1%) were between 0 and 2 °C and/or between 8 and 25 °C for more than 30 min. In conclusion, once dispensed to patients, most thermolabile drugs are improperly stored. Future studies should focus on clinical consequences and possible solutions.

Pre-plasticization of thermal binder facilitates processing and granule growth during melt granulation of gabapentin using co-rotating twin screw extruder

Plasticization, a common method of reducing the polymer melt viscosity in plastics extrusion, was investigated to improve the processability of a pharmaceutical formulation during twin-screw melt granulation. The thermolabile drug gabapentin was used as a model compound given previous work showed the benefit of preparing 80% drug loading gabapentin granules with hydroxypropyl cellulose as thermal binder. The plasticizer triethyl citrate was selected based on physicochemical compatibility with both the thermal binder and gabapentin by assessing polymer melt rheology and drug stability, respectively. Gabapentin was melt granulated at 80% drug loading with pre-plasticized binder using a co-rotating twin-screw extruder. The chemical stability and tabletability of the pre-plasticized granules were assessed to evaluate granule tabletability, drug stability, and process robustness. The granulation of gabapentin was facilitated by pre-plasticization, showing both increased granule growth and the ability to optimize processing conditions by lowering processing temperature. Pre-plasticization of thermal binder was therefore shown to be beneficial during melt granulation as a method of optimizing processing conditions while maintaining granule robustness.

Preparation and characterization of polypills containing aspirin and simvastatin using 3D printing technology for the prevention of cardiovascular diseases

Three-dimensional (3D) printing has become a promising manufacturing technique for pharmaceutical products. Fused deposition modeling (FDM) is the most affordable printing technology. But this technique has two major drawbacks: limited drug-loading capacity and the stability of thermolabile drugs. So, other techniques such as melt casting could be associated with FDM to overcome these limitations. In the melt casting method, the drug is mixed with a molten polymer and is poured in the mold and allowed to solidify. The present study for the first time describes the preparation of a multi-compartment polypill permits the physical separation of incompatible drugs by combination of FDM and melt casting techniques. A two-compartment polypill was made using FDM by Eudragit® L100-55 and simultaneously its compartments were filled by aspirin and simvastatin containing molten PEG 6000. Simultaneous usage of FDM and melt casting techniques could increase the drug-loading capacity of 3D-printed polypills. The low temperatures used in melt casting and the absence of solvent in this method would warrant the integrity of polypills, the complete separation of incompatible drugs, and their stability. The prepared polypills showed good uniformity in drug content which confirms the precision of FDM and melt casting techniques. Drug interaction was investigated before and after the accelerated stability test using DSC, which showed that 3D-printed polypills successfully preserved drugs from the interaction. For the first time, this study demonstrates the feasibility of the combination of FDM and melt casting techniques as an innovative platform for CVD polypills production.

3D Printed Drug Delivery Systems Based on Natural Products.

In the last few years, the employment of 3D printing technologies in the manufacture of drug delivery systems has increased, due to the advantages that they offer for personalized medicine. Thus, the possibility of producing sophisticated and tailor-made structures loaded with drugs intended for tissue engineering and optimizing the drug dose is particularly interesting in the case of pediatric and geriatric population. Natural products provide a wide range of advantages for their application as pharmaceutical excipients, as well as in scaffolds purposed for tissue engineering prepared by 3D printing technologies. The ability of biopolymers to form hydrogels is exploited in pressure assisted microsyringe and inkjet techniques, resulting in suitable porous matrices for the printing of living cells, as well as thermolabile drugs. In this review, we analyze the 3D printing technologies employed for the preparation of drug delivery systems based on natural products. Moreover, the 3D printed drug delivery systems containing natural products are described, highlighting the advantages offered by these types of excipients.

Comparative evaluation of 2% turmeric extract with nanocarrier and 1% chlorhexidine gel as an adjunct to scaling and root planing in patients with chronic periodontitis: A pilot randomized controlled clinical trial.

Context:Nanoparticles, owing to their smaller size, penetrate regions inaccessible to other delivery systems, such as periodontal pockets. Thus, the present study aimed to comparatively evaluate efficacy of 2% curcumin with nanocarrier and 1% chlorhexidine gel as a local drug delivery (LDD) in the treatment of periodontal pockets.Materials and Methods:Forty-five chronic periodontitis patients with pocket depth 5–7 mm in two or more teeth were selected. Full-mouth scaling and root planing (SRP) was done for all patients followed by random allocation to the three treatment groups, namely SRP group (Group 1), 2% curcumin with nanogel (Group 2), and 1% chlorhexidine gel (Group 3). Clinical parameter assessment and microbiological analysis of subgingival plaque samples for Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Tannerella forsythia (Tf) was done at baseline, 21st day, and 45th day.Results:The results showed that when the two LDD agents were used as an adjunct to SRP in chronic periodontitis, there was an improvement in all clinical parameters. Evaluation of microbiological parameters also showed a significant reduction in Aa, Pg, and Tf levels. Comparison of 2% turmeric extract with a nanocarrier system with 1% chlorhexidine gel showed that both the agents had a comparable antibacterial effect on the three selected periodontopathic bacteria.Conclusion:The present study showed that both the LDD agents showed an effective improvement of clinical and microbiologic parameters. 2% curcumin delivered with a nanocarrier system showed results comparable to chlorhexidine gel and hence shows promising future as an LDD agent in the treatment of periodontal pockets.

The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products

Currently in the pharmaceutical industry, continuous manufacturing is an area of significant interest. In particular, hot-melt extrusion (HME) offers many advantages and has been shown to significantly reduce the number of processing steps relative to a conventional product manufacturing line. To control product quality during HME without process interruption, integration of inline analytical technology is critical. Vibrational spectroscopy (Raman, NIR and FT-IR) is often employed and used for real-time measurements because of the non-destructive and rapid nature of these analytical techniques. However, the establishment of reliable Process Analytical Technology (PAT) tools for HME of thermolabile drugs is challenging. Indeed, the Raman effect is inherently weak and might be subject to interference. Moreover, during HME, heating and photodecomposition can occur and disrupt spectra acquisition. The aim of this research article was to explore the use of inline Raman spectroscopy to characterise a thermolabile drug, ramipril (RMP), during continuous HME processing. Offline measurements by HPLC, LC-MS and Raman spectroscopy were used to characterise RMP and its main degradation product, ramipril-diketopiperazine (RMP-DKP, impurity K). A set of HME experiments together with inline Raman spectroscopic analyses were performed. The feasibility of implementing inline Raman spectroscopic analysis to quantify the level of RMP and RMP-DKP in the extrudate was addressed. Two regions in the Raman spectrum were selected to differentiate RMP and RMP-DKP. When regions were combined, a principle component analysis (PCA) model defined by these two main components (PC 1 = 50.1% and PC 2 = 45%) was established. Using HPLC analyses, we were able to confirm that the PC 1 score was attributed to the level of RMP-DKP, and the PC 2 score was related to the RMP drug content. Investigation of the PCA scatterplot indicated that HME processing temperature was not the only factor causing RMP degradation. Additionally, the plasticiser content, feeding speed and screw rotating speed contributed to RMP degradation during HME processing.

Screening of Silk Fibroin as a Stabilizer for Freeze Drying of Thermolabile Drug

Screening of Silk Fibroin as a Stabilizer for Freeze Drying of Thermolabile Drug

Development of a dual extrusion printing technique for an acid- and thermo-labile drug

Over the last years fused deposition modeling has been increasingly considered as a game-changing technique for the preparation of individualized pharmaceutical products. Until now investigations have mainly focused on dosage forms loaded with very stable drugs or model substances. Going beyond this early stage of research, developers will also have to deal with more challenging active substances. In this work different printing designs for tablets containing the acid- and thermo-labile drug pantoprazole sodium were tested. Initial dual extrusion printing of a cellulose acetate phthalate coat and a tablet core of polyethylene glycol 6000 with 10% (m/m) pantoprazole sodium resulted in thermal degradation of pantoprazole at cellulose acetate phthalate printing temperatures of 141 °C. Therefore, different tablet designs were developed. The sectioning of the design of the tablet coat in a gastro-resistant cellulose acetate phthalate bottom part and an upper nearly insoluble polycaprolactone part printed at only 58 °C was suitable to prevent visible signs of thermal degradation. Dissolution testing indicated also no drug loss during dual extrusion printing. However, printed enteric tablets with shell thicknesses of 0.4 to 0.5 mm were not completely gastro-resistant. Drug release at intestinal pH values was delayed compared to uncoated cores. In conclusion, 3D-printing of gastro-resistant tablets containing thermo- and acid-labile drugs seems in principle possible. However, it remains an unsolved challenge to meet United States Pharmacopeia requirements.

Low temperature fused deposition modeling (FDM) 3D printing of thermolabile drugs

Fused deposition modelling (FDM) is the most commonly investigated 3D printing technology for the manufacture of personalized medicines, however, the high temperatures used in the process limit its wider application. The objective of this study was to print low-melting and thermolabile drugs by reducing the FDM printing temperature. Two immediate release polymers, Kollidon VA64 and Kollidon 12PF were investigated as potential candidates for low-temperature FDM printing. Ramipril was used as the model low melting temperature drug (109 °C); to the authors’ knowledge this is the lowest melting point drug investigated to date by FDM printing. Filaments loaded with 3% drug were obtained by hot melt extrusion at 70 °C and ramipril printlets with a dose equivalent of 8.8 mg were printed at 90 °C. HPLC analysis confirmed that the drug was stable with no signs of degradation and dissolution studies revealed that drug release from the printlets reached 100% within 20–30 min. Variable temperature Raman and solid state nuclear magnetic resonance (SSNMR) spectroscopy techniques were used to evaluate drug stability over the processing temperature range. These data indicated that ramipril did not undergo degradation below its melting point (which is above the processing temperature range: 70–90 °C) but it was transformed into the impurity diketopiperazine upon exposure to temperatures higher than its melting point. The use of the excipients Kollidon VA64 and Kollidon 12PF in FDM was further validated by printing with the drug 4-aminosalicylic acid (4-ASA), which in previous work was reported to undergo degradation in FDM printing, but here it was found to be stable. This work demonstrates that the selection and use of new excipients can overcome one of the major disadvantages in FDM printing, drug degradation due to thermal heating, making this technology suitable for drugs with lower melting temperatures.

Comparative FTIR, Compaction and In vitro Dissolution Studies of Plectranthus esculentus Modified Starches in Metronidazole Tablet Formulations by Direct Compression

Wet and dry granulation methods for tablet manufacturing tend to be problematic for thermolabile and moisture sensitive drugs, and few excipients are available for use in direct compression (DC) due to stringent requirements. This study aimed to evaluate the drug/excipients compatibility, compaction and in vitro dissolution properties of Plectranthus esculentus modified starches in tablets using metronidazole as a model drug by DC. Native starch extracted from P. esculentus was modified by three methods and we produced three modified starches namely; acid hydrolyzed P. esculentus starch (APS), pregelatinized P. esculentus starch (PPS), and ethanol dehydrated pregelatinized P. esculentus starch (PPE). For drug/excipient compatibility studies, Fourier Transform Infrared Spectroscopy (FTIR) was used. Powder compaction was evaluated using Heckel model, while in vitro dissolution studies were conducted using USP basket method. The starches were evaluated in comparison with microcrystalline cellulose (MCC PH 101). The FTIR peaks revealed no interaction of these excipients with the drug. Compaction studies indicate that the modifications yielded starches of comparable compact behaviors with MCC PH 101 especially APS and PPE, they both plastically deformed with PPE producing the hardest tablets. APS and PPS disintegrate faster 2.83 and 1.42 min respectively which were significantly different from the disintegration time of MCC PH 101 and PPE which are higher 35.34 and 45.53 min respectively. For the in vitro dissolution, APS and PPS, their T50 and T90 were achieved in less than 10 min, T50 and T90 for PPE were achieved at 38 and 58 min respectively, while for MCC PH 101 both T50 and T90 were not observed after 60 min. APS produced metronidazole tablets of better quality in terms crushing strength, friability and drug-release profile. Acid hydrolysis of P. esculentus starch produced good directly compressible excipient that can be use in DC for immediate release tablet formulations.