Nonionic Drug Research Articles

Predictions of biorelevant solubility change during dispersion and digestion of lipid-based formulations

Computational approaches are increasingly explored in development of drug products, including the development of lipid-based formulations (LBFs), to assess their feasibility for achieving adequate oral absorption at an early stage. This study investigated the use of computational pharmaceutics approaches to predict solubility changes of poorly soluble drugs during dispersion and digestion in biorelevant media. Concentrations of 30 poorly water-soluble drugs were determined pre- and post-digestion with in-line UV probes using the MicroDISS Profiler™. Generally, cationic drugs displayed higher drug concentrations post-digestion, whereas for non-ionized drugs there was no discernible trend between drug concentration in dispersed and digested phase. In the case of anionic drugs there tended to be a decrease or no change in the drug concentration post-digestion. Partial least squares modelling was used to identify the molecular descriptors and drug properties which predict changes in solubility ratio in long-chain LBF pre-digestion (R2 of calibration = 0.80, Q2 of validation = 0.64) and post-digestion (R2 of calibration = 0.76, Q2 of validation = 0.72). Furthermore, multiple linear regression equations were developed to facilitate prediction of the solubility ratio pre- and post-digestion. Applying three molecular descriptors (melting point, LogD, and number of aromatic rings) these equations showed good predictivity (pre-digestion R2 = 0.70, and post-digestion R2 = 0.68). The model developed will support a computationally guided LBF strategy for emerging poorly water-soluble drugs by predicting biorelevant solubility changes during dispersion and digestion. This facilitates a more data-informed developability decision making and subsequently facilitates a more efficient use of formulation screening resources.

DEVELOPMENT AND CHARACTERIZATION OF FLURBIPROFEN LOADED NIOSOMAL IN-SITU GEL FOR OPHTHALMIC DRUG DELIVERY SYSTEM

Niosome are non-ionic surfactant-based liposomes, obtained in the hydration of artificial non-ionic surfactants, without or with addition of cholesterol or additional lipids. The intention of the current study was to organize and evaluate the in-situ niosomal gel loaded with flurbeprofen for the ophthalmic drug delivery system. Flurbeprofen, a nonsteroidal anti- infammatory drug (NSAIDs) is used to relief pain and inflammation. It carries out anti- inflammatory, analgesic and antipyretic activities. Flurbeprofen loaded Niosomes investigate the connection among the non-ionic drug / surfactant ratio with the adding of cholesterol was successfully organized with the thin film hydration way and compare the result of different grade of span used (20, 40 and 60) with the different ratio of cholesterol. Niosomes have been identified by drug entrapment efficiency, drug content, particle size and in-vitro diffusion study. Niosomes prepared using span 60 and cholesterol in the ratio (1:1) f4 showed greater entrapment efficiency (79.2%).

Electrically controlled transdermal drug release of ionic and non-ionic drug from kappa-iota carrageenan cryogel

The goals of this study were to fabricate and characterize the kappa (K) and iota (I) carrageenan (CAR) cryogel matrix for electrically controlled transdermal ionic namely diclofenac (DCNa) and non-ionic namely theophylline (Theo) delivery. The CAR cryogels were prepared by freeze-drying method based on the effects of CAR types which were different sulfate ester group content in the structure, K-CAR concentrations, and blending K and I-CAR. According to the results, the increasing K-CAR concentrations affected to reduce the swelling behavior and pore size of cryogels. However, the swelling behavior was increased and pore size was decreased with blending K/I-CAR. The release mechanism of DCNa and Theo was a non-fickian and fickian diffusion depending on drug types, cryogels composition, and applied electric potentials. The amount of drug release was decreased with increasing K-CAR concentrations and decreased with a blending K/I-CAR. However, the amount of drug release was increased with increasing electric potential, especially an anionic drug. The amount of DCNa was higher than that of Theo with and without applied electric potential. The maximum amount of drug release was 78.06 and 58.78% for DCNa and Theo, respectively. Thus, the CAR cryogel is suitable for controlled release of ionic and non-ionic drug with and without applied electric field.

Interactions of Surfactants with Biomimetic Membranes-2. Generation of Electric Potential with Non-Ionic Surfactants.

It is known that noncharged surfactants lead to electric effects that interact with biomimetic membranes made of nitrocellulose filters, which are impregnated with fatty acid esters. At a surfactant concentration as low as 64 micrometers in one of the solutions, they lead to the transient formation of transmembrane electric potential. Maximum changes of this potential are proportional to the log of noncharged surfactant concentrations when it changes by three orders of magnitude. We explain this new and nontrivial effect in terms of an earlier suggested physicochemical mechanics approach and noncharged surfactants transient changes induced by membrane permeability for inorganic ions. It could be used to imitate the interactions of non-ionic drugs with biological membranes. The effect may also be used in determining the concentration of these surfactants and other non-ionic chemicals of concern, such as pharmaceuticals and personal care products.

Synthesis and release behavior of layered double hydroxides\u2013carbamazepine composites

Carbamazepine (CBZ) was incorporated into layered double hydroxides (LDH) to be used as a controlled drug system in solid tumors. CBZ has a formal charge of zero, so its incorporation in the anionic clay implies a challenge. Aiming to overcome this problem, CBZ was loaded into LDH with sodium cholate (SC), a surfactant with negative charge and, for comparison, without SC by the reconstruction method. Surprisingly, it was found that both resultant nanocomposites had similar CBZ encapsulation efficiency, around 75%, and the LDH-CBZ system without SC showed a better performance in relation to the release kinetics of CBZ in simulated body fluid (pH 7.4) and acetate buffer simulating the cellular cytoplasm (pH 4.8) than the system with SC. The CBZ dimensions were measured with Chem3D and, according to the basal spacing obtained from X-ray patterns, it can be arranged in the LDH-CBZ system as a monolayer with the long axis parallel to the LDH layers. Fourier transform infrared spectroscopy and solid state NMR measurements confirmed the presence of the drug, and thermogravimetric analyses showed an enhanced thermal stability for CBZ. These results have interesting implications since they increase the spectrum of LDH application as a controlled drug system to a large number of nonionic drugs, without the addition of other components.

NIOSOMES AS AN APPROACH TO IMPROVE THE SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS II DRUGS

Based on their solubility and permeability, drugs are typically divided into four classes (Classes I–IV) according to the biopharmaceutics classification system (BCS). Of these classes, BCS class II drugs have high permeability and low solubility; not only do these characteristics constitute the rate-limiting step in the formulation of these drugs but the low solubility in water results in low bioavailability. Thus, methods for improving their solubility have been developed using lipid carriers such as liposomes, niosomes, and aquasomes; other approaches include self-micro-emulsifying drug delivery systems (SMEDDS) and self-nano-emulsifying drug delivery systems (SNEDDS). Currently, niosome-based drug delivery systems that utilize nonionic surfactants, drugs, and cholesterol in varying ratios are being widely used to deliver both hydrophilic and lipophilic drugs in addition to several other applications of niosomes.

ROSUVASTATIN CALCIUM PRONIOSOME POWDER: A NOVEL APPROACH TO IMPROVE INTESTINAL ABSORPTION AND BIOAVAILABILITY

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of rosuvastatin calcium by improving solubility, dissolution, and/or intestinal permeability.
 Methods: Proniosomal powder formulations were prepared with rosuvastatin calcium drug varying the Span 40 and cholesterol ratio in the range of 0.8:0.2–0.2:0.8 using maltodextrin as carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug:Span 40 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study, and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies.
 Results: Physicochemical studies help in optimization of formulations. Enhancement in dissolution is due to incorporation of rosuvastatin calcium into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control.
 Conclusion: Proniosomes provide a powerful and functional way of distribution of inadequately soluble rosuvastatin calcium drug which is proved from in vivo studies based on the enhanced oral delivery.

FORMULATION AND EVALUATION OF OPTIMISED MALTODEXTRIN BASED PRONIOSOME POWDERS CONTAINING BAZEDOXIFENE ACETATE FOR ORAL DELIVERY

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of bazedoxifene acetate by improving solubility, dissolution and/or intestinal permeability.
 Methods: Proniosomal powder formulations were prepared with bazedoxifene acetate drug varying the span 40 and cholesterol ratio in the range of 0.8:0.2 to 0.2:0.8 using maltodextrin as a carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug: span 40 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies.
 Results: Physico-chemical studies help in the optimization of formulations. Enhancement in dissolution is due to the incorporation of bazedoxifene acetate into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Ex vivo studies show significant permeation enhancement across the gastrointestinal membrane compared to control.
 Conclusion: In conclusion, proniosomes provide a powerful and functional way of the distribution of inadequately soluble bazedoxifene acetate drug, which is proved from in vivo studies based on the enhanced oral delivery.

ENHANCED INTESTINAL ABSORPTION AND BIOAVAILABILITY VIA PRONIOSOMES FOR BAZEDOXIFENE ACETATE DRUG

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of bazedoxifene acetate by improving solubility, dissolution and intestinal permeability.
 Methods: Proniosomal powder formulations were prepared with bazedoxifene acetate drug varying the span 60 and cholesterol ratio in the range of 0.8:0.2 to 0.2:0.8 using maltodextrin as carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug: span 60 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies.
 Results: Physico-chemical studies among various formulations helped in optimization of batch. Good flow properties confirmed from angle of repose values indicate easy filling into capsules. Enhancement in dissolution is due to incorporation of bazedoxifene acetate into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Solid state characterization studies prove the transformation to amorphous form with small particle size improving permeation. No drug excipient interaction was observed and sample is stable in refrigerated conditions. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control. Invivo studies proved enhanced absorption of bazedoxifene acetate drug by oral route.
 Conclusion: In conclusion, proniosomes provide a powerful and functional way of distribution of inadequately soluble bazedoxifene acetate drug which is proved from in vivo studies based on the enhanced oral delivery.

Electrically controlled release of anticancer drug 5-fluorouracil from carboxymethyl cellulose hydrogels

Transdermal drug delivery is a technique used to introduce a drug through the skin and into the blood system. The drug-matrix hydrogels based on carboxymethyl cellulose (CMC) were prepared by solution casting method using citric acid as the crosslinking agent at various amounts. The 5-fluorouracil, an anticancer non-ionic drug, was released from the CMC hydrogels under applied electrical field. The diffusion coefficient and the release mechanism of the drug of the CMC hydrogels were investigated by the modified Franz-diffusion cell with the PBS buffer solution at the pH value of 7.4 and at 37 °C for the duration of 24 h. The effects of mesh size, electric potential, and electrode polarity were systematically investigated. The swelling test illustrated an increase in the mesh size with decreasing crosslinking agent. In addition, the drug diffusion coefficient increased with decreasing crosslinker: repeated group mole ratio. The diffusion coefficient depended critically on the applied electric potential and the electrode polarity. The non-ionic drug release mechanisms were identified as the matrix deswelling and electroosmosis, in addition to the pure diffusion without electric field. Thus, CMC has been shown a potential bio-based matrix for electrically controlled non-ionic drug delivery.

Ionic Polymethacrylate Based Delivery Systems: Effect of Carrier Topology and Drug Loading.

The presented drug delivery polymeric systems (DDS), i.e., conjugates and self-assemblies, based on grafted and star-shaped polymethacrylates have been studied for the last few years in our group. This minireview is focused on the relationship of polymer structure to drug conjugation/entrapment efficiency and release capability. Both graft and linear polymers containing trimethylammonium groups showed the ability to release the pharmaceutical anions by ionic exchange, but in aqueous solution they were also self-assembled into nanoparticles with encapsulated nonionic drugs. Star-shaped polymers functionalized with ionizable amine/carboxylic groups were investigated for drug conjugation via ketimine/amide linkers. However, only the conjugates of polybases were water-soluble, giving opportunity for release studies, whereas the self-assembling polyacidic stars were encapsulated with the model drugs. Depending on the type of drug loading in the polymer matrix, their release rates were ordered as follows: Physical ≥ ionic > covalent. The studies indicated that the well-defined ionic polymethacrylates, including poly(ionic liquid)s, are advantageous for designing macromolecular carriers due to the variety of structural parameters, which are efficient for tuning of drug loading and release behavior in respect to the specific drug interactions.

Choline based polymethacrylate matrix with pharmaceutical cations as co-delivery system for antibacterial and anti-inflammatory combined therapy

Anionic drugs, i.e. salicylate (Sal−) and sulfacetamide (Sfc−) were chosen as counterions in trimethylammonium based poly(meth)acrylates. These ionic systems with amphiphilic properties were used to form polymeric systems for dual drug delivery by loading of nonionic pharmaceutics like immunosuppressant quercetin (QUE), anti-inflammatory indomethacin (IMC) and antibiotic erythromycin (ERY). The latter one was loaded with high efficiency (>60%), whereas poorer loading efficiency was obtained for aromatic compounds (<10%) because of strong repulsing effect with ionic moieties in polymer matrix. Coordinating and polar properties of anions as the additional factors in drug-polymer affinity can be applied to adjust the drug loading and release. The polymer particles resulted in aqueous solutions were characterized by hydrodynamic diameters (70–430 nm) and zeta potentials (20–65 mV) indicating specific multifactor action/contraction of drug delivery system (DDS) components. The release profiles of both type drugs demonstrated typical diffusion process with burst effect during initial 2 h, and then it slowed down for next 80 h. The release rate of bioactive anions in the dual system was not affected by the presence of nonionic drug showing comparable kinetics profile with the analogical single drug system carrying ionic drug. The most promising Sal-based and ERY-loaded polymer system was able to release ~60% of ionic drug (via exchange with phosphate anions in buffer solution) and ~70% of nonionic drug. The biological studies on the proposed polymeric systems were conducted indicating no toxic activity against human cells (NHDF and BEAS-2B), no gene expression for anti-inflammatory interleukins IL6 and IL8 as well as the antibacterial activity was observed against E. coli.

The use of immobilized artificial membrane chromatography to predict bioconcentration of pharmaceutical compounds

The potential of immobilized artificial membrane chromatography (IAM) to predict bioconcentration factors (BCF) of pharmaceutical compounds in aquatic organisms was studied. For this purpose, retention factors extrapolated to pure aqueous phase, logkw(IAM), of 27 drugs were measured on an IAM stationary phase, IAM.PC.MG type. The data were combined with retention factors on two IAM columns, IAM.PC.MG and IAM.PC.DD2 types, reported previously by our research group and correlated with logBCF values predicted by Estimation Program Interface (EPI Suite) Software. Linear models were established upon exclusion of ionic or highly hydrophilic nonionic drugs, for which a constant value of logBCF equal to 0.50 was arbitrarily assigned by EPI Suite Software. As additional physicochemical parameter BioWin5 proved to be statistically significant, expressing the decrease of bioaccumulation potential as a result of biodegradation in the aquatic environment. The constructed IAM model was successfully validated by application to a set of pharmaceuticals, whose experimental BCF values are available. Better predictions compared to EPI Suite Software were achieved for the dataset under study. Since bioconcentration process involves electrostatic interactions, IAM retention may be a better measure for BCF values, especially for ionic species, compared to octanol-water partition coefficients widely implemented in environmental sciences. The developed approach can be considered as a novel tool for the prediction of bioconcentration of pharmaceutical compounds in aquatic organisms in order to minimize further experimental assays in the future.

Optimal choice of ionic and nonionic iron drugs for the treatment of iron deficiency anemia in pregnancy

У статті висвітлені актуальні проблеми лікування залізодефіцитної анемії (ЗДА). Наведені основні механізми і етапи розвитку захворювання. На підставі даних літератури виконано порівняльний аналіз ефективності та безпеки феротерапії препаратами іонного і неіонного заліза, до яких належать препарати гідроксид-полімальтозного комплексу тривалентного заліза. Визначено основні особливості лікування ЗДА. Гепсидин є основним регуляторним пептидом, який забезпечує гомеостаз заліза в організмі. Наукові пошуки тривають, і невдовзі ми ще більше наблизимось до розуміння механізмів його забезпечення. При лікуванні ЗДА у вагітних і породіль повинні бути дотримані принципи індивідуалізованого підходу з призначенням високодозових засобів заліза, що дають виражений клінічний ефект при малій вірогідності побічної дії. Добру перспективу для застосування при лікуванні ЗДА в жінок мають засоби, що створені на основі гідроксид-полімальтозного комплексу. Лікування ЗДА повинно тривати не тільки до нормалізації показників периферійної крові, а й до відновлення заліза в тканинах (депо). За можливості, паралельно призначенню засобів заліза усувають причину виникнення ЗДА. Застосування гідроксид-полімальтозних комплексів заліза супроводжується мінімальними побічними ефектами, що значно підвищує комплаєнтність лікування: неухильне дотримання пацієнтами призначених програм терапії залізодефіцитних станів, виконання повного обсягу призначень і термінів лікування ЗДА покращує якість життя хворих і прискорює їхнє одужання. Перший етап лікування пероральними засобами заліза має тривати до повного відновлення рівня гемоглобіну, кількості еритроцитів, показника гематокриту і складає в середньому 1,5–2 міс. Наступний етап – насичення депо заліза, що триває 2–3 міс. Після насичення депо заліза дозу препаратів зменшують до 30–60 мг/доба. Критерієм ефективності лікування препаратами заліза при ЗДА є поява ретикулоцитозу в периферійній крові на 5–7-й день від початку терапії. Непрямим свідченням ефективного лікування препаратами заліза є підвищення концентрації гемоглобіну щодоби на 1 г/л.

A Comparison of Buffered and Non-Buffered 2% Lidocaine With Epinephrine, a Pilot Study

Lidocaine with vasoconstrictors are acidic, pH 3.5, to extend shelf-life and are buffered by the patient's tissue fluids to a neutral pH once injected. Only the non-ionized drug form crosses the nerve membrane to effect anesthesia. At pH 7.4 less than half of the drug dosage is the unionized form, pKa 8. Buffering lidocaine with bicarbonate just prior to injection maximizes the active drug available to the nerve trunk resulting in faster onset and, deeper anesthetic effect. With a neutral pH pain also is reduced on injection (1,2). However, a limited number of clinical studies address the topic.

Pharmaceutical salts: Theory, use in solid dosage forms and in situ preparation in an aerosol

In this article, the theoretical foundation for salts is given with an emphasis on the amount of drug in solution. Consideration is given for the solubility of the non-ionized form, acid dissociation constant and solubility product, which are the limiting constraints. For dissolution of nonionized drugs, the surface pH differs from the bulk pH, giving rise to a lower than expected rate. For salts, theoretical considerations are relatively complex, and an experimental approach to estimating the surface pH is more likely to be of value in predicting the dissolution rate. General guidelines are described for screening, preparing and characterizing drugs as salts, which critically depend on the goal of the product development. Thereafter, our work involving the preparation of salts as a means to generate aerosols from a solution is provided. The solubility of six structurally related compounds was determined in four acids. Thereafter, the amount of the compound in solution was determined as a function of pH, using the acid that provided the highest solubility. Because the pH required to achieve the needed concentration for aerosol generation was low, ammonia vapor was introduced into the air stream to neutralize aerosol droplets. Solvent was then removed from the aerosol by a silica column. The resulting aerosol had a concentration of 96 µg/l and a mass median particle size of 1.8 µm. The reported pharmacokinetic study substantiated the feasibility of evaluating its safety and efficacy of inhalation administration in the rat model.

Water Solubility of Complexes between a Peptide Mixture and Poorly Water-Soluble Ionic and Nonionic Drugs

Water Solubility of Complexes between a Peptide Mixture and Poorly Water-Soluble Ionic and Nonionic Drugs

Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation.

In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs.

Comparison of ionic and non-ionic drug release from multi-membrane spherical aerogels

The presented research was oriented towards the preparation of dry biodegradable alginate aerogels with multi-membranes using a multi-step sol-gel process with potential applications as carriers during oral drug delivery. First alginate spherical hydrogels were formed in CaCl2 or BaCl2 solutions by ionic cross-linking. These cores were further immersed into alginate sodium solution, filtered through a sieve, and dropped into the salt solution again. Multi-membrane hydrogels were obtained by repeating the above process. They were further converted into aerogels by supercritical drying. The effect of the number of membranes was investigated regarding the loading and release of the model drugs nicotinic acid and theophylline. Moreover, the efficiencies of Ba(2+) and Ca(2+) metal ions for forming tridimensional networks that retain and extend drug release were also investigated. Nicotinic acid release was prolonged by adding membranes around the core and using Ca(2+) for cross-linking. However, retarded theophylline release was only obtained by using Ba(2+) for cross-linking. Namely, by increasing the number of membranes and BaCl2 concentration drug release became linear versus time in all studied cases. In the case of nicotinic acid loading increased by adding membranes around the core, however, for theophylline the opposite results were obtained due to the different nature of the model drugs.

Investigation of griseofulvin and hydroxypropylmethyl cellulose acetate succinate miscibility in ball milled solid dispersions

Solid dispersions of varying weight ratios compositions of the nonionic drug, griseofulvin and the hydrophilic, anionic polymer, hydroxylpropylmethyl cellulose acetate succinate, have been prepared by ball milling and the resulting samples characterized using a combination of Fourier transform infra-red spectroscopy, X-ray powder diffraction and differential scanning calorimetry. The results suggest that griseofulvin forms hydrogen bonds with the hydroxylpropylmethyl cellulose acetate succinate polymer when prepared in the form of a solid dispersion but not when prepared in a physical mixture of the same composition. As anticipated, the actual measured glass transition temperature of the solid dispersions displayed a linear relationship between that predicted using the Gordon-Taylor and Fox equations assuming ideal mixing, but interestingly only at griseofulvin contents less than 50 wt%. At griseofulvin concentrations greater than this, the measured glass transition temperature of the solid dispersions was almost constant. Furthermore, the crystalline content of the solid dispersions, as determined by differential scanning calorimetry and X-ray powder diffraction followed a similar trend in that the crystalline content significantly decreased at ratios less than 50 wt% of griseofulvin. When the physical mixtures of griseofulvin and the hydroxylpropylmethyl cellulose acetate succinate polymer were analyzed using the Flory-Huggins model, a negative free energy of mixing with an interaction parameter of -0.23 were obtained. Taken together these results suggest that anionic hydrophilic hydroxylpropylmethyl cellulose acetate succinate polymer is a good solvent for crystalline nonionic griseofulvin with the solubility of griseofulvin in the solid dispersion being was estimated to be within the range 40-50 wt%. Below this solubility limit, the amorphous drug exists as amorphous glassy solution while above these values the system is supersaturated and glassy suspension and solution may coexist.