The aim of this research was to develop a solid dosage form containing 1.5 g of the pesticide cypermethrin. The dosage should be stable in a tropical climate. In addition, it is to disintegrate and disperse in 10 L of tap water within 3 minutes. Such dissolution should yield a 150 ppm dispersion of cypermethrin, stable for at least one week. This provides for a dip dispersion to treat ticks and fly infestation on livestock. A new solid dosage was formulated as the scope of this research. It is a gel-based solid dosage form. Polymer electrolyte ASP4 - a copolymer of methacrylic acid, ethyl acrylate and diethyl maleate, was used to produce the gel. Preliminary tests revealed that ASP4- based gel, on its own, failed to meet the required dissolution time of 3 minutes. Strong entanglements of ASP4 chains impeded rapid dissolution. These strong entanglements occurred owing to the use of a high concentration of ASP4. Reducing the concentration of ASP4 yielded a solution of high viscosity instead of a gel. It was therefore decided to Gel-based solid dosage form for pesticide delivery use a superabsorbent (Product Z1069) in conjunction with ASP4 to produce the gel. Product Z1069 is a cross-linked sodium polyacrylate. Before producing the gel, a 1:1.5 by mass oil/water (O/W) emulsion was prepared using the phase-inversion route. The water (W) phase comprised 85.9% distilled water, 3.9% ASP4 at 20% dispersion, 8.6% sodium carbonate (0.5 M) and 1.6% Emulsogen EL. All concentrations are indicated in mass %. The oil (O) phase consisted of 76.9% cypermethrin, 19.3% Solvesso S200 and 3.8% Phenyl Sulphonate CA, also by mass. This emulsion was gelled by adding the superabsorbent Product Z1069 (ca. 37.5% by mass relative to the W phase of the emulsion). The superabsorbent strongly absorbed water, depleting it from the emulsion. This resulted in an increase of the effective concentration of ASP4 in the water phase of the emulsion. This increase of the polymer electrolyte concentration brought about a gel-like state corresponding to the desired solid dosage form. Rheometry confirmed that the dosage form maintained a solid gel-like consistency at 50°C. The dosage contained 24.6% m/m cypermethrin. Thus, the required dosage of 1.5 g was achieved in pellets weighing ca. 6.1 g. Such pellets rapidly disintegrated with mild stirring in 10 L of tap water. Complete pellet disintegration and active dispersion occurred within 2.5 minutes at ambient temperature (25 ± 2°C). / Dissertation (MSc)--University of Pretoria, 2008. / Chemistry / unrestricted

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2017-04-03T16:42:21Z No. of bitstreams: 1 Ventura, Danielle Martins [Dissertação, 2011].pdf: 1094934 bytes, checksum: 7f527e246ec0bc1d24d1c492dc672bbe (MD5) / Made available in DSpace on 2017-04-03T16:42:22Z (GMT). No. of bitstreams: 1 Ventura, Danielle Martins [Dissertação, 2011].pdf: 1094934 bytes, checksum: 7f527e246ec0bc1d24d1c492dc672bbe (MD5) / As formas farmacêuticas líquidas são as mais adequadas para uso em pediatria e em pacientes que não conseguem deglutir comprimidos, pois além de apresentarem maior flexibilidade no ajuste da dose, facilitam a administração dos medicamentos. Como a maioria dos medicamentos disponíveis no mercado está na forma de comprimidos e cápsulas, o recurso utilizado no ambiente hospitalar para contornar as necessidades terapêuticas exclusivas de alguns pacientes é a transformação de formas farmacêuticas (TFF). A literatura apresenta poucos estudos relacionados à estabilidade das formulações produzidas através desta prática, fazendo com que ocorra a utilização empírica dessas formulações. O presente trabalho teve como objetivo desenvolver uma formulação de suspensão de Hidroclorotiazida (HCTZ) a partir de comprimidos de diferentes origens, através de TFF, a ser manipulada em ambiente hospitalar. Para tanto, utilizou-se uma formulação proposta por TAGLIARI (2008), estabelecida para a preparação de suspensões de HCTZ a partir insumo farmacêutico ativo, a fim de se avaliar a aplicabilidade desta formulação às suspensões produzidas por TFF. A formulação proposta tem como composição do veículo suspensor: Carboximetilcelulose sódica (CMC-Na) (0,6%), Glicerina (2%), Benzoato de sódio (0,1%) ácido cítrico e água, mostrando-se estável por mais de 120 dias. Neste trabalho, assumiu-se que as preparações decorrentes da prática de TFF são consideradas preparações extemporâneas e portanto, apresentam prazo de validade de 48 horas, sendo este o período determinado para realização dos ensaios de caracterização. Foram utilizados comprimidos de 4 fabricantes diferentes, sendo que para um deles (FA) utilizou-se comprimidos de 2 dosagens, apresentando as seguintes nomenclaturas: FA1(HCTZ 25mg), FA2 (HCTZ 50mg), FB(HCTZ 25mg), FC (HCTZ 25mg) e FD (HCTZ 50mg). Foi realizada a caracterização desses comprimidos, no qual se determinou o peso médio e o teor, segundo compêndios oficiais, e após a trituração dos mesmos, verificou-se a densidade e a granulometria dos pós obtidos. Os comprimidos de FC apresentaram teor acima do preconizado pela Farmacopeia Brasileira. Porém, optou-se por mante-los no estudo, mediante a correção da quantidade de pó a ser utilizada no preparo das suspensões. As suspensões de HCTZ a 2,5mg/mL foram preparadas utilizando CMC-Na a 0,6% (p/v) como agente suspensor. As formulações produzidas foram avaliadas quanto ao volume de sedimentação e redispersibilidade. Os resultados obtidos nestes ensaios indicaram que as suspensões não apresentavam estabilidade física apropriada, sendo necessária a realização da adequação da formulação proposta. Foram preparadas então, suspensões com veículo suspensor contendo diferentes concentrações de CMC-Na (0,2%, 0,3%, 0,4%, 0,5% e 0,6%) para todos comprimidos utilizados na primeira etapa. As preparações obtidas foram analisadas quanto ao volume de sedimentação, redispersibilidade, comportamento reológico e potencial zeta. O teste de volume de sedimentação mostrou grandes diferenças em todas as suspensões estudadas, diferindo na velocidade de sedimentação e no volume de sedimento formado, sendo estes dependentes da concentração do polímero utilizada. A redispersibilidade foi estudada em dois períodos: após 2 e 7 dias de repouso, sendo semelhantes os resultados encontrados nos dois períodos. Neste teste, os resultados apontaram grandes diferenças na redispersão das formulações, indicando que quanto maior concentração do polímero, mais tempo a preparação levou para ficar homogênea. Na análise do comportamento reológico, todas as formulações estudadas apresentaram fluxo não-newtoniano pseudoplástico, mostrando-se dependente da concentração do polímero utilizada. O potencial zeta obtido nestas preparações indicou a que as suspensões apresentaram-se floculadas. As diferenças apresentadas nos testes realizados indicaram que os diferentes excipientes presentes nas formulações dos comprimidos utilizados, interferiram na estabilidade física das preparações, não sendo possível estabelecer uma formulação a ser utilizada para todos os comprimidos, numa preparação obtida por TFF. Diante disso, foi eleita a formulação de melhor estabilidade física para cada comprimido estudado, e procedeu-se a analise do teor destas formulações. Para tanto, utilizou-se a metodologia analítica farmacopeica, que demonstrou ser especifica, linear, exata, precisa e robusta, dentro das condições experimentais estudadas. As formulações produzidas a partir de TFF apresentaram teor dentro do critério de aceitação proposto / The liquid dosage forms are suitable for use in children and in patients who can’t swallow pills, because it have greater flexibility in dose adjustment and ease the administration of medicines. Like most drugs on the market is in the form of tablets and capsules, the resource used in hospitals to circumvent the unique therapeutic needs of some patients is the transformation of pharmaceutical forms (TPF). The literature contains few studies related to the stability of the formulations produced by this practice, allowing it to empirical use of these formulations. This study aimed to develop a suspension formulation of hydrochlorothiazide (HCTZ) from tablets of different sources through TPF, to be manipulated in a hospital environment. For this purpose, we used a formulation proposed by Tagliari (2008), established for the preparation of suspensions of HCTZ from active pharmaceutical ingredient, in order to evaluate the applicability of this formulation produced by TFF. The proposed formulation has the composition of the vehicle hanger: sodium carboxymethylcellulose (CMC-Na) (0.6%), glycerin (2%), sodium benzoate (0.1%) citric acid and water, being stable for more of 120 days. In this work, it was assumed that the preparations from the practice of TFF preparations are considered untimely and therefore have shelf life of 48 hours, this being the period of time to achieve the characterization tests. The tablets were used from four different manufacturers, and for one (FA) was used two doses of pills, with the following classifications: FA1 (HCTZ 25 mg), FA2 (HCTZ 50 mg), FB (HCTZ 25 mg), FC (HCTZ 25mg) and FD (HCTZ 50 mg). We performed the characterization of these tablets, which determined the weight and content, according to official compendia, and after grinding the same, there was the density and particle size of powders obtained. FC tablets showed above the level recommended by the Brazilian Pharmacopoeia. However, it was decided to keep them in the study, by correction of the amount of powder to be used in the preparation of suspensions. Suspensions of HCTZ to 2.5 mg/mL were prepared using CMC-Na 0.6% (w/v) as an agent hanger. The formulations produced were evaluated for the amount of sedimentation and redispersibilidade. The results from these tests indicated that the suspensions had no proper physical stability, being necessary to perform the suitability of the proposed formulation. Were then prepared, with vehicle suspensions suspensor containing different concentrations of CMC-Na (0.2%, 0.3%, 0.4%, 0.5% and 0.6%) for all tablets used in the first step. The preparations obtained were analyzed for the amount of sedimentation, redispersibilidade, zeta potential and rheological behavior. The sedimentation volume test showed significant differences in all the suspensions studied, differing in sedimentation rate and volume of sediment formed, which are dependent on the concentration of the polymer used. The redispersibilidade was studied in two periods: after 2 and 7 days of rest, the results were similar in both periods. In this test, the results showed great differences in the redispersion of the formulations, indicating that the higher concentration of the polymer, the preparation took more time to be homogeneous. In the analysis of rheological behavior, all the formulations studied showed non-Newtonian pseudoplastic flow, being dependent on the concentration of the polymer used. The zeta potential obtained in these preparations indicated that the suspensions had to flocculate. The differences in the tests indicated that the different excipients present in formulations of tablets used, influenced the physical stability of the preparations, it is not possible to establish a formulation to be used for all tablets, a preparation obtained by TPF. Thereat, the better physical stability for each formulation studied was elected, and we proceeded to analyze the content of these formulations. For this purpose, we used the analytical methodology pharmacopoeia, which proved to be specific, linear, accurate, precise and robust, within the experimental conditions studied. The formulations produced from TPF content presented within the proposed acceptance criterion

Controlled-release formulations for pesticide applications act as depot systems that continuously release the active ingredients into the environment over a speci ed period, usually from months to years. However, some applications require fast-dissolving drug delivery. The interest of this research is in fast-release of water-insoluble pesticides into aquatic environments. This study considered the use of dextrin starch and urea eutectics as fast release, solid dosage carrier forms that contain an active ingredient. The chosen active for this study is an acaricide called amitraz (N-methylbis-(2,4-xylyliminomethyl)- methylamine). The focus is on matrix-based dosage forms such as tablets, granules or bres that either disintegrate or dissolve to release a water-insoluble active. These types of dosage forms can be fabricated using processes such as lyophilisation, spray drying, solvent casting, hot melt extrusion, compression moulding, wet granulation, compaction and electrospinning. A simple melt-casting procedure has been discussed in the present work. Dextrin is a water-soluble form of partially hydrolysed starch and is a promising candidate matrix material for dissolving solid dosage forms. The molecular weight of the dextrin was analysed with MALDI-TOF methods and rheological relations. Glycerolplasticized thermoplastic dextrin-based nanocomposites were prepared with a twin-screw extrusion-compounding process. The nano llers included a layered double hydroxide (LDH), cellulose nano bres (CNF) and stearic acid. The time-dependent retrogradation of the compounds was monitored by X-ray di raction (XRD) and dynamic mechanical thermal analysis (DMA). XRD showed that the inclusion of stearic acid in the formulations led to the formation of an amylose-lipid complex and a stable crystallinity during ageing. Dissolution rates in water for samples containing dextrin starch, were characterised using an iodine indicator and UV-visible spectroscopy. High pressure di erential scanning calorimetry (HPDSC) indicated that the addition of stearic acid led to the formation of amylose-lipid complexes (ALC's). An additive system containing stearic acid and CNF was deemed suitable for compounding with amitraz. Compounding at temperatures above the melting point of the latter led, on dissolution in water, to the release of much ner particles of the acaricide, which was con rmed with particle size analysis (PSA). The addition of the acaricide caused an apparent increase in the dissolution rate of the thermoplastic dextrin. Two eutectic urea systems were considered for casting with amitraz. A eutectic system of urea and acetamide was found to display a melting point of 44 C at a 37 wt.% urea composition. The other system consisting of urea and 1,3-dimethylurea displayed a eutectic point at 32 wt.% urea composition which melted at 59 C. Di erential scanning calorimetry (DSC), however, con rmed a melting point depression due to a high moisture content caused by the compounds high hygroscopicity. The endotherm of the sample containing no excess moisture showed a melting point of 70 C. The 1,3-dimethylurea system was deemed suitable for casting with amitraz. XRD of the eutectic composition indicated a small amount of co-crystallisation. The samples were cast as disks of various diameters while keeping the height of the disks constant. The creation of the cast disks showed automatic generation of a nely dispersed form of the active through the process of melting the deep eutectic solvent, the dissolution of the active and its phase separation on cooling and solidi cation of the eutectic. This implies that ne grinding of the actives might not be necessary. Eutectic casts containing 20 wt.% amitraz dissolved at a slower rate than casts not containing the hydrophobic active ingredient. The advantageous features of these casts were exempli ed using the acaricide incorporated into the urea & 1,3-dimethylurea eutectic. This work provides two safe, biodegradable and water soluble materials for use as a matrix to contain active ingredients. One material, the eutectic organic salt casts, can be produced at low temperatures (<100 C) and can be directly cast into storage containers. The complete dissolution of the cast compounded with a hydrophilic active is rapid (4-6 min). The second material, a thermoplastic dextrin, was melt compounded in an extruder at temperatures not exceeding 120 C. This compound containing 20 wt.% of the active dissolved over a 12 hour period. Dextrin, known to be widely used as an adhesive, will aid in the adhesion of the active ingredient to the surface where it must be used. / Dissertation (MEng (Chemical Engineering))--University of Pretoria, 2020. / PAMSA / Department of Science and Innovation under Grant DST/CON 0004/2019 / Chemical Engineering / MEng (Chemical Engineering) / Unrestricted

Dosage forms have been developed over the years for various applications. The dosage form consists of the active drug in combination with pharmaceutical excipients. The pharmaceutical excipients solubilise, suspend, thicken, dilute, emulsify, stabilise, preserve, colour and flavour medicinal agents into efficacious and appealing dosage forms. The dosage form under investigation in this study is of the oral type. The Pheroid® is a unique drug delivery system which consists of an oil-in-water emulsion system. Emulsion based drug systems provide a suitable medium for the delivery of both hydrophobic and hydrophilic drugs which can be incorporated into its oil or water phase for delivery to the site of action. These advantages make them more efficient as dosage form. Emulgels are either emulsion of oil-in-water or water-in-oil type, which is gelled by mixing with gelling agents. Incorporation of emulsion into gel increases its stability and makes it a dual control release system. The presence of the gel phase makes it a non-greasy formulation which favours good patient compliance. A strategy followed to improve the stability of the emulgel system is the packaging of the formula into single dose sachets to protect the product against physical and chemical breakdown during patient usage. All factors such as selection of gelling agent, preservatives and formulation methods influencing the stability and efficacy of Pheroid® emulgel are discussed. In this study, three different emulsifiers were added to the formula and the analysis of visual appearance, pH measurements, rheological studies, light microscopy and confocol laser scanning microscopy (CLSM) will provide an insight to the potential usage of emulgel as drug delivery system. A range of para-hydroxybenzoate esters was tested in the Pheroid® emulgel and the most suitable candidate chosen for further accelerated stability testing. It was thus possible to prepare a single dose emulgel with Carbopol® 934P (0.2% w/v) as an emulsifier, with Nipastat® (0.175% w/v) and PG (10% v/v) as preservatives into a stable dosage form suitable for further product development. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Dosage forms have been developed over the years for various applications. The dosage form consists of the active drug in combination with pharmaceutical excipients. The pharmaceutical excipients solubilise, suspend, thicken, dilute, emulsify, stabilise, preserve, colour and flavour medicinal agents into efficacious and appealing dosage forms. The dosage form under investigation in this study is of the oral type. The Pheroid® is a unique drug delivery system which consists of an oil-in-water emulsion system. Emulsion based drug systems provide a suitable medium for the delivery of both hydrophobic and hydrophilic drugs which can be incorporated into its oil or water phase for delivery to the site of action. These advantages make them more efficient as dosage form. Emulgels are either emulsion of oil-in-water or water-in-oil type, which is gelled by mixing with gelling agents. Incorporation of emulsion into gel increases its stability and makes it a dual control release system. The presence of the gel phase makes it a non-greasy formulation which favours good patient compliance. A strategy followed to improve the stability of the emulgel system is the packaging of the formula into single dose sachets to protect the product against physical and chemical breakdown during patient usage. All factors such as selection of gelling agent, preservatives and formulation methods influencing the stability and efficacy of Pheroid® emulgel are discussed. In this study, three different emulsifiers were added to the formula and the analysis of visual appearance, pH measurements, rheological studies, light microscopy and confocol laser scanning microscopy (CLSM) will provide an insight to the potential usage of emulgel as drug delivery system. A range of para-hydroxybenzoate esters was tested in the Pheroid® emulgel and the most suitable candidate chosen for further accelerated stability testing. It was thus possible to prepare a single dose emulgel with Carbopol® 934P (0.2% w/v) as an emulsifier, with Nipastat® (0.175% w/v) and PG (10% v/v) as preservatives into a stable dosage form suitable for further product development. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Drug delivery systems (DDS) are essentially pharmaceutical products for human therapy, typically involving a mixture of active ingredients and excipients. Based upon quantitative characterization of structure, the thesis introduces the concept of classifying the architecture of DDS into four levels by their spatial scale and the life time period. The primary level is recognised as the static structure of the whole dosage form with a size from μm to cm with the final structure generated by formulation design. The secondary level categorises the structures of particles or sub-units to form a DDS with sizes from nm to mm as key units in processing such as mixing, grinding, granulation and packing; The tertiary level represents the dynamic structures of DDS during the drug release phase in vitro or in vivo incorporating the structure size range from nm to mm, which undergo changes during dissolution, swelling, erosion or diffusion. The spatial scale for the quaternary level is defined as the meso or micro scale architecture of active and non-active molecules within a DDS with sizes from Å to μm for the molecular structure of drug and excipients. Methods combining X-ray tomography, image processing, and 3D reconstructions have been devised and evaluated to study systematically pharmaceutical structures and correlate them with drug release kinetics of DDS. Based on the quantitative structural information of pharmaceutical intermediates and dosage forms, it is possible now to correlate structures with production processing, behaviour and function, and the static and dynamic structures of DDS with the release kinetics. Thus, a structure-guided methodology has been established for the research of DDS. / Chinese Academy of Sciences

Twin screw wet granulation (TSG) has been studied as a continuous manufacturing alternative to batch granulation for nearly twenty years. One of the main differences between batch granulation and TSG lies in the exiting granules being presented as a bimodal particle size distribution (PSD) in the latter case. Current process analytical technologies (PAT) can monitor a monomodal distribution well but there have been no techniques disclosed in the public domain so far that can accurately monitor this unusually shaped PSD. Acoustic emissions (AE) has been identified as a PAT of interest due to its ease of use (lack of calibration), low cost, and non-invasive design relative to other PATs used for monitoring PSDs. Hence the goal of this thesis was to develop AE as a process analytical technology (PAT) capable of estimating the full distribution of produced granules by TSG in real time. The first research study of this thesis focused on the development of the new technology. The AE PAT consisted of an acoustic sensor, an impact plate, and software to convert the time-domain signal of particle collisions into a time-averaged frequency-domain spectrum to be subsequently used to estimate a weight-averaged particle size distribution. A novel and much required addition to the PAT was inclusion of a digital filter based on particle mechanics parameters to overcome auditory masking which hindered accurately converting the cumulative sounds of impact into a PSD. The PAT was tested in this study with granulated lactose monohydrate and with the new digital filter, obtaining a maximum error of 1 wt% across all particle sizes tested. In the second research study, as more formulations commonly used in the industry were tested, the filter proved unable by itself to account for the differences in impact mechanics and therefore needed to be modified to incorporate the more inelastic behaviour now being seen. Two micromechanical models were explored, and the Walton-and-Braun model was found to be the most suitable for the AE PAT – reducing its error from 8 wt% down to 2.75 wt% across four formulations producing coefficients of restitution from 0.79 to 0.24. In the last research study in this thesis, the now-functional inline PAT was used to reveal mechanistic details related to the transition state in granulation as a TSG starts up, to improve the field’s understanding of the granulation mechanism. The technique was able to estimate the PSD over much shorter periods of material collection compared to sieving, allowing the evolution of the PSD as a function of time to be examined for varying degrees of fill (DF) and liquid-to-solids ratios. It was determined that the time to steady state, at both DF tested, occurred at approximately 5 times the mean residence time of the process by both PAT and sieving analyses. Particle sizes between 102-2230 μm were then tracked as a function of time below 120 s and variations of granule growth were seen for each degree of fill which added to the understanding of the granulation mechanism. This PAT shows great promise as a monitoring tool to implement quality by design principles for TSG in pharmaceutical manufacturing. / Thesis / Doctor of Philosophy (PhD)

No description available.

No / This work explored the role of skin appendages (shunt route) in passive and iontophoretic drug and liposome penetration. The technique used an epidermis and stratum corneum sandwich from the same skin donor with the additional stratum corneum forming the top layer of the sandwich. Penetration was monitored during occluded passive and iontophoretic (0.5 mA cm-2) delivery of mannitol and estradiol solutions, and ultradeformable liposomes containing estradiol. The shunt route had a significant role during passive penetration of mannitol (hydrophilic compound), but was negligible during penetration of estradiol (lipophilic drug) and liposomes. In iontophoresis, the shunt route significantly contributed to the overall flux of all preparations, being highest for mannitol. However, shunts were not the only pathway for iontophoretic drug delivery and evidence was observed for the creation of new aqueous pathways via disorganization of the intercellular lipid domain of stratum corneum. The skin sandwich technique should prove valuable for general studies on routes of skin penetration.

This dissertation has focused on the solid-state characterization of different co-crystal system as well as the effect of co-crystallization of these systems on pharmaceutical dosage form performance. Urea/ 2-MB, caffeine/ malonic acid, caffeine/ oxalic acid and theophylline/ malonic acid co-crystals were prepared using co-grinding- and co-precipitation techniques. In addition, the synthesis of co-crystals through two novel methods has been demonstrated. This includes compaction and convection mixing. The solid-state characterization of the co-crystals has been carried out using XRPD, Raman spectroscopy, DSC, TGA, hot-stage microscopy and SEM. After preparation of co-crystals, tablets have been produced from co-ground-, co-precipitated-, and physical mixtures using Compaction Studies Press (Kaleva), and the data were recorded to compare between the different mixtures, regarding compactibilty, compressibility and deformational properties. The DSC results showed that the physical mixtures of all systems, formed co-crystals during heating process. For systems of urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid, the co-ground mixture produced tablets with higher tensile strength compared with either co-precipitated or physical mixture. However, for caffeine/ oxalic acid system, the tensile strengths of compacts produced from the physical mixture were greater than those obtained from either co-ground or co-precipitated mixtures. The Heckel data suggested that urea/ 2-MB, caffeine/ malonic acid and theophylline/ malonic acid systems are Type 1 materials, as an extensive linearity during compression was indicative of a plastic deformation mechanism, while the caffeine/ oxalic acid system was Type 2 materials. However, the co-precipitated mixture of urea/ 2-MB system was the least compressible, as it possessed the greatest value of yield pressure (85 MPa) and the highest elastic recovery (7.42%). The co-precipitated mixture of both of caffeine/ malonic acid and theophylline/ malonic acid systems was the most compressible with small yield pressure values of (44 & 80 MPa) and elastic recovery of (7.2% & 6.56%), respectively. The co-ground mixture of caffeine/ oxalic acid possessed the highest value of yield pressure (166 MPa) and thus the lowest compressibility among other mixtures. Furthermore, the addition of microcrystalline cellulose and α-lactose monohydrate has affected the crystallinity as well as the tableting properties of the co-crystals. After the addition of excipients, the tensile strength of compacts was about 2 times higher than any other mixture. Finally, urea/ 2-MB and caffeine/ malonic acid co-crystals were successfully synthesized through convection mixing and compaction.