PACAP(6-38) inhibits the growth of prostate cancer cells

The human recombinant granulocyte colony-stimulating factor (rhG-CSF) is largely used in the treatment of neutropenia occurring during chemotherapy. After injection, this glycoprotein distributes through the whole body. Thus, to obtain high and durable bone marrow concentrations, targeting with polyalkylcyanoacrylate nanoparticles was considered. Two methods of preparation were investigated: anionic polymerization and precipitation of the preformed polymer. By anionic polymerization, it was possible to associate more than 66% of rhG-CSF with nanoparticles (polyisobutyl- or polyisohexylcyanoacrylate nanoparticles) when the glycoprotein was added at the end of the polymerization process. It has been shown that the rhG-CSF was mainly adsorbed on the surface of the nanoparticles and most of the colony stimulating activity was conserved. Using precipitation of performed polyisohexylcyanoacrylate, 90% of rhG-CSF was associated with nanoparticles, the protein being mainly adsorbed onto the nanoparticle surface. In this case, a decrease of the colony stimulating activity was however observed. Whatever the method used, the in vitro release of rhG-CSF from the polyisohexylcyanoacrylate nanoparticles, was progressive during 8 h in seric conditions. Nevertheless, using mice as an animal model, it has been shown that the short-term effects of intravenously injected rhG-CSF were not increased by its association with polyisohexylcyanoacrylate nanoparticles.     

Screening of Australian medicinal plants for antiviral activity

The nanoencapsulation of a model protein drug, bovine serum albumin (BSA), using gelatin as the matrix material is reported. Nanoencapsulation was conducted using a modified water-in-oil (w/o) emulsion method, which is emulsifier-free and simple. The nanoencapsulation product, BSA-containing gelatin nanoparticles, is characterized in terms of nanoparticle morphology, size and size distribution, water content, and in vitro protein release. The BSA-containing gelatin nanoparticles obtained from this nanoencapsulation process are nearly spherical and have a log-normal size distribution. The average diameter of the BSA-containing gelatin nanoparticles is approximately 840 nm. They can absorb 51-72% of water. In vitro release experiments demonstrate that BSA has been successfully encapsulated in, and can be released from the gelatin nanoparticles. The release of BSA from the gelatin nanoparticulate matrix follows a diffusion-controlled release mechanism. It is found that temperature affects both the water content and the BSA release rate of the gelatin nanoparticles.     

Physico-chemical characterization, preparation and performance of poly (methylidene malonate 2.1.2) nanoparticles

The present investigation confirms that initially implemented procedure to produce poly(methylidene malonate 2.1.2) (PMM 2.1.2) nanoparticles (Lescure et al. Pharm Res 1994;11:1270-77) lead to products mostly containing plasticizing oligomers which strongly lowered glass-transition temperature (Tg), dramatically reduced nanoparticle consistency and rendered them too sensitive to solubilization when diluted in an aqueous medium. From MALDI-TOF spectroscopy analysis, performed on intact colloids, emerged some structural information about these oligomeric species which could result from an intramolecular cyclization mechanism occurring soon in the course of the polymerization process. Thus, with the objective of overcoming these drawbacks, this contribution deals with the variations of manufacturing specifications such as pH and magnetic stirring speed to try and modulate molecular weight (MW) of nanoparticle constituents and reduce oligomer concentration. Although the analyses performed on these new nanoparticles were rather encouraging, the colloid formation yield became so low that it required the development of other methodologies, excluding a previous emulsion step, and allowing a controlled production of PMM 2.1.2-made nanoparticles having better physico-chemical characteristics while keeping good pharmaceutical capabilities.     

Preparation, characterization and in vitro antimicrobial activity of ampicillin-loaded polyethylcyanoacrylate nanoparticles

In this paper, the experimental conditions for preparing ampicillin-loaded polyethylcyanoacrylate (PECA) nanoparticles are described. The effects of drug concentration and surfactant type in the polymerization medium on the particle size distribution and loading capacity were studied. The results of these studies show that only the type of surfactant has an impact on the nanoparticle dimensions. The release rate of ampicillin from PECA nanoparticles at pH 7.4 (extracellular value pH) performed either with and without esterases, show that the drug release is considerably increased in the presence of these exzymes. The results of drug release study at pH 1.1 (simulated gastric juice) are very interesting. This study has evidenced that the 70% of ampicillin is released quickly, while the remaining fraction is firmly incorporated in nanoparticles. The released ampicillin is quickly degraded in acid medium while the entrapped fraction is protected from acid degradation and afterwards, when nanoparticles reach the small intestine, can be readily released in the presence of esterases. This result could be exploited for the oral administration of the ampicillin-PECA system. Finally, studies of antimicrobial activity of prepared systems evidenced that ampicillin-loaded PECA nanoparticles exhibit an activity equal or higher than the free drug.     

PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug

The nanoprecipitation technique for preparation of nanoparticles suffers the drawback of poor incorporation of water soluble drugs. The aim of this study was therefore to assess various formulation parameters to enhance the incorporation of a water soluble drug (procaine hydrochloride) into poly(dl-lactide-co-glycolide) (PLGA) nanoparticles prepared by this technique. Approaches investigated for drug incorporation efficiency enhancement included the influence of aqueous phase pH, replacement of procaine hydrochloride with procaine dihydrate and the inclusion of excipients: poly(dl-lactide) (PLA) oligomers, poly(methyl methacrylate-co-methacrylic acid) (PMMA-MA) or fatty acids into the formulation. The nanoparticles produced were submicron size (<210 nm) and of low polydispersity. It was found that an aqueous phase pH of 9.3, replacement of procaine hydrochloride with procaine dihydrate and the incorporation of PMMA-MA, lauric and caprylic acid into the formulation could enhance drug incorporation efficiency without the size, morphology and nanoparticle recovery being adversely influenced. For instance changing the aqueous phase pH from 5.8 to 9.3 increased nanoparticle recovery from 65.1 to 93.4%, drug content from 0.3 to 1.3% w/w and drug entrapment from 11.0 to 58.2%. However, the presence of high ratios of lauric acid and procaine dihydrate in the formulation adversely affected the morphology and size of the nanoparticles. Also, PLA oligomers were not considered a feasible approach since it decreased drug entrapment from 11.0 to 8.4% and nanoparticle recovery from 65.1 to 19.6%. Drug release from nanoparticles appears to consist of two components with an initial rapid release followed by a slower exponential stage. This study has demonstrated that formulation variables can be exploited in order to enhance the incorporation of a water soluble drug into PLGA nanoparticles by the nanoprecipitation technique.     

Poly(vinyl alcohol) nanoparticles prepared by freezing-thawing process for protein/peptide drug delivery

Poly(vinyl alcohol) (PVA) hydrogel nanoparticles have been prepared by using a water-in-oil emulsion technology plus cyclic freezing-thawing process. The PVA hydrogel nanoparticles prepared by this method are suitable for protein/peptide drug delivery since formation of the hydrogel does not require crosslinking agents or other adjuvants and does not involve any residual monomer. Particularly, there is no emulsifier involved in this new method. Bovine serum albumin (BSA), as a model protein drug, is incorporated into the PVA hydrogel nanoparticles. The PVA hydrogel nanoparticles possess a skewed or log-normal size distribution. The average diameter of the PVA hydrogel nanoparticles is 675.5+/-42.7 nm. Protein drug loading efficiency in the PVA hydrogel nanoparticles is 96.2+/-3.8%. The PVA hydrogel nanoparticles swell in an aqueous solution and the swelling degree increases with the increase of temperature. In vitro release studies show that the BSA release from the nanoparticles can be prolonged to 30 h. The BSA release follows a diffusion-controlled mechanism. The number of freezing-thawing cycle and release temperature both influence BSA release rate considerably. Less freezing-thawing cycle or higher release temperature leads to faster drug release. The BSA is stable during preparation of the PVA hydrogel nanoparticles.     

Glycine-activated chloride currents of neurons freshly isolated from the ventral tegmental area of rats

This paper describes the preparation and characterisation of poly(lactide-co-glycolide) (PLG) nanoparticles containing the enzyme L-asparaginase. L-Asparaginase was encapsulated in PLG nanospheres using a water-in-oil-in-water solvent evaporation technique. The effect of the copolymer molecular weight and the presence of carboxyl-end groups in the copolymer chain on the physicochemical and in vitro release properties of the nanoparticles was investigated. Results indicated that size, encapsulation efficiency and in vitro release properties (enzymatic activity retention and protein quantification) of the nanoparticles were affected by the PLG molecular weight. As expected, nanoparticles made of high-molecular-weight PLG had a larger size, a higher loading and la slower release rate than those made od a low-molecular-weight PLG. Nevertheless, the most relevant factor affecting the entrapment and release of L-asparaginase from PLG nanoparticles was the presence of free carboxyl-end groups in the PLG chain. The nanoparticles made of PLG with free carboxyl-end groups had a high protein loading (4.86%, w/w) and provided a continuous delivery of the active enzyme for 20 days. However, the enzyme loading was lower (2.65%, w/v) and no active enzyme was detected in the release medium after a 14-day incubation period when nanoparticles were made of PLG with carboxyl-end groups esterified. These results give evidence of the potential of PLG nanospheres for the continuous delivery of L-asparaginase for extended periods of time and show the effect of the PLG chain end-groups in the amount and activity of the enzyme loaded into the nanospheres.     

Evaluation of process parameters involved in chitosan microsphere preparation by the o/w/o multiple emulsion method

Chitosans are interesting biopolymers largely studied for applications in the medical and pharmaceutical fields. In this work, an o/w/o multiple emulsion technique was used for the preparation of hydrophobic drug loaded microspheres. Moreover, the influence of critical variables (concentration of acetic acid in the polymer solution and drug-polymer ratio) on microsphere morphology and drug content was evaluated. Two chitosans of different molecular weights and deacetylation degree were employed; ketoprofen, a non-steroidal anti- inflammatory drug, was chosen as the hydrophobic model drug. The multiple emulsion method produced well-formed microspheres with good yields. Acetic acid concentration in the polymeric solutions influenced particle size and drug content of the microspheres. The highest drug encapsulation efficiencies were obtained for the lowest theoretical drug/chitosan ratio.     

Encoding, repetition, and the mirror effect in recognition memory: symmetry in motion

The entrapment of loperamide hydrochloride (LPM) in biodegradable polymeric drug carriers such as nanoparticles might enable its passage across the blood-brain barrier. The optimization of the preparation of the LPM-loaded PLA nanoparticles was performed employing high pressure emulsification-solvent evaporation. The resulting nanoparticles were characterized by particle size, distribution, thermal analysis, and drug release profiles. The partition of LPM into the organic phase increased with an increase in pH of the aqueous phase and with addition of lipophilic surfactants such as sorbitan fatty acid esters, resulting in an increase in the drug entrapment in the nanoparticles. Evaporation of the organic phase under reduced pressure and the addition of ethanol in the organic phase yielded a high drug entrapment due to the rapid polymer precipitation. The addition of the sorbitan fatty acid esters further increased the drug entrapment even at higher LPM concentrations. The results of thermal analysis suggest that LPM was homogeneously dispersed in the amorphous polymer matrix. The in vitro release of the drug from nanoparticles was biphasic, with a fast initial phase, followed by a second slower phase. Different drug release profiles from nanoparticles can be achieved by addition of sorbitan fatty acid esters, or the employment of different solvents as the organic phase.     

In vitro degradation study of polyester microspheres by a new HPLC method for monomer release determination

Biodegradable polyesters have increasing importance as materials used for the preparation of microspheres. The knowledge of their degradation process is important to prepare microparticulate delivery systems with suitable drug release rates. In this work an in vitro degradation study of empty and drug loaded microspheres is described. Three different polyesters were used: two poly-d, l-lactides of different molecular weight and a poly-d, l-lactide-co-glycolide (50:50). Diazepam has been chosen as the model drug. Solvent evaporation and spray-drying were used as preparation methods. To study the polymer degradation process, a new HPLC method is proposed for the direct and (in the case of the copolymer) simultaneous determination of the monomer(s): lactic acid (LA) and glycolic acid (GA). SEM and particle size analysis highlight the different characteristics of the particles, depending on their preparation method: spray-dried spheres result to be always smaller with respect to particles obtained by solvent evaporation. The results obtained indicate in particular that: the preparation methods play an important role in determining the degradation behaviour of microspheres, as unloaded spray-dried particles are characterized by a higher monomer release rate with respect to microspheres obtained by solvent evaporation; PLGA spheres degrade faster than PDLLA microparticles, according to the higher hydrophilicity of the copolymer; the two monomers are released at a different rate in the case of PLGA (faster for GA, slower for LA); the presence of diazepam increases the polymer degradation rate, with respect to empty particles.     

Differential in vitro hepatic and intestinal metabolism of ifosfamide in the rat

Influence of chitosan molecular weight on drug loading and drug release of drug-loaded chitosan microspheres was studied. Chitosans of 70,000 (LC), 750,000 (MC), and 2,000,000 (HC) molecular weight were employed alone or as mixtures (HC/LC 1:1-1:2 w/w). Ketoprofen (ket) was chosen as the model drug to be encapsulated. Microspheres characterized by different theoretical polymer/drug ratios were prepared (2:1, 1:1, 1:2 w/w). Satisfactory ket contents were obtained for all batches of chitosan microspheres with the theoretical polymer/drug ratio 1:2 w/w; microspheres made of HC/LC (1:2 w/w) were characterized by good drug content and encapsulation efficiency independent by polymer/drug ratio. Prepared chitosan microparticulate delivery systems can modulate ket release within 48 hr. Microspheres consisting of HC/LC (1:2 w/w) were the most suitable formulation in controlling drug release.     

Stabilization of 10-hydroxycamptothecin in poly(lactide-co-glycolide) microsphere delivery vehicles

PURPOSE: The purpose of this study was to investigate the potential of poly(lactide-co-glycolide) (PLGA) microspheres to stabilize and deliver the analogue of camptothecin, 10-hydroxycamptothecin (10-HCPT). METHODS: 10-HCPT was encapsulated in PLGA 50:50 microspheres by using an oil-in-water emulsion-solvent evaporation method. The influence of encapsulation conditions (i.e., polymer molecular weight (Mw), polymer concentration, and carrier solvent composition) on the release of 10-HCPT from microspheres at 37 degrees C under perfect sink conditions was examined. Analysis of the drug stability in the microspheres was performed by two methods: i) by extraction of 10-HCPT from microspheres and ii) by sampling release media before lactone--carboxylate conversion could take place. RESULTS: Microspheres made of low Mw polymer (inherent viscosity 0.15 dl/g) exhibited more continuous drug release than those prepared from polymers of higher Mw (i.v. = 0.58 and 1.07 dl/g). In addition, a high polymer concentration and the presence of cosolvent in the carrier solution to dissolve 10-HCPT were both necessary in the microsphere preparation in order to eliminate a large initial burst of the released 10-HCPT. An optimal microsphere formulation released 10-HCPT slowly and continuously for over two months with a relatively small initial burst of the released drug. Both analytical methods used to assess the stability of 10-HCPT revealed that the unreleased camptothecin analogue in the microspheres remained in its active lactone form (> 95%) over the entire 2-month duration of study. CONCLUSIONS: PLGA carriers such as those described here may be clinically useful to stabilize and deliver camptothecins for the treatment of cancer.     

Arterial uptake of biodegradable nanoparticles: effect of surface modifications

Restenosis is the reobstruction of an artery following interventional procedures such as balloon angioplasty or stenting. Local pharmacotherapeutic approaches using controlled release systems are under investigation to inhibit the regional pathophysiologic process of restenosis. We have been investigating biodegradable nanoparticles (100 +/- 39 nm in diameter, mean +/- sd) for the local intra-arterial drug delivery. The purpose of this study was to investigate nanoparticle surface modifications (see Table 1) to enhance their arterial uptake. The PLGA (polylactic polyglycolic acid copolymer) nanoparticles were formulated by an oil-in-water emulsion solvent evaporation technique using a 2-aminochromone (U-86983, Upjohn and Pharmacia) (U-86) as a model antiproliferative agent. The various formulations of nanoparticles were evaluated for the arterial wall uptake by using an ex-vivo dog femoral artery model. The selected formulations were then tested in vivo in acute dog femoral artery and pig coronary artery models. The nanoparticles surface modified with a cationic compound, didodecyldimethylammonium bromide (DMAB), demonstrated 7-10-fold greater arterial U-86 levels compared to the unmodified nanoparticles in different ex-vivo and in-vivo studies. The mean U-86 levels were 10.7 +/- 1.7 microg/10 mg (dog) and 6.6 +/- 0.6 microg/10 mg (pig) in the artery segments ( approximately 2 cm) which were infused with the nanoparticles. The pig coronary studies further demonstrated that the infusion of nanoparticles with higher U-86 loading reduced the arterial U-86 levels, whereas increasing the nanoparticle concentration in the infusion solutions increased the arterial U-86 levels. The biodistribution studies in pigs following coronary arterial administration of nanoparticles demonstrated disposition of U-86 in the myocardium and distally in the liver and the lung. The mechanism of enhanced arterial uptake of the DMAB surface modified nanoparticles seems to be due to the alteration in the nanoparticle surface charge. The unmodified nanoparticles had a zeta potential of -27.8 +/- 0.5 mV (mean +/- sem, n = 5), whereas the DMAB modified nanoparticles demonstrated a zeta potential of +22.1 +/- 3.2 mV (mean +/- sem, n = 5). The adsorption of DMAB to the nanoparticle surface followed the Freundlich isotherm with binding capacity k = 28.1 microg/mg and affinity constant p = 2. 33. In conclusion, surface modified nanoparticles have potential applications for intra-arterial drug delivery to localize therapeutic agents in the arterial wall to inhibit restenosis.     

Minimally invasive coronary surgery at the beginning of the new millennium

Several formulations of poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic-co-glycolic acid) (PLGA) nanocapsules containing phenylbutazone were prepared according to the interfacial deposition technique. These formulations differed in the type of polymer used to form the shell of the nanocapsules. Analysis of particle size distribution and encapsulation efficiency of the nanocapsules revealed that the type and molecular weight of polyester used were the main factors influencing these properties. PLA had the highest encapsulation efficiency with the best reproducibility. From in vitro release studies, a small amount of drug release was observed at pH 7.4. However, in the gastric medium, an important burst effect occurred and was highest with the PLGAs and lowest with PCL, suggesting that drug release from these systems is affected by the type of polymer and the environmental conditions. The two formulations of phenylbutazone-loaded nanocapsules should be evaluated based on PCL and PLA in vivo in order to determine to what extent they are able to reduce the local side effects of this drug.     

Prolonged release of tegafur from S/O/W multiple emulsion

To develop a prolonged and sustained release preparation, we prepared an albumin microsphere-in-oil-in-water emulsion (S/O/W) and examined sustained release from it in comparison with other control preparations such as water-in-oil (W/O) emulsions and microspheres in vitro and in vivo, respectively. Tegafur was used as a model drug. A microsphere-in-oil emulsion was prepared by adding albumin microspheres to soybean oil containing 20% Span 80. To prepare an S/O/W emulsion, the microsphere-in-oil emulsion was added into an aqueous solution of hydroxypropyl methylcellulose containing Pluronic F68. The mean particle size of the albumin microspheres was 3 microns, and the ratio of entrapment of tegafur into albumin microspheres was about 25%. In an in vitro release test, the t75 of the S/O/W emulsion was fourfold greater and in an in vivo release test the mean residence time of tegafur from the S/O/W emulsion was more than twofold that from a W/O emulsion or microsphere system. The mean residence time of 5-fluorouracil (5-FU) from an S/O/W emulsion was also greater than with other dosage forms. These results suggest the possible usefulness of an S/O/W emulsion for the sustained and prolonged release of tegafur.     

Progress in the design of DNA sequence-specific lexitropsins

Polymeric microparticles containing two ceftiofur salts as antimicrobial agents for intramammary application in dry cows were prepared by modified o/w-solvent evaporation methods (dispersion or cosolvent method) or by a w/o/w-multiple emulsion solvent evaporation method. The microspheres were characterized with respect to drug loading, drug release, and morphological properties. The three methods resulted in high encapsulation efficiencies. The choice of organic solvent/solvent mixture strongly affected the structure of the microparticles; both matrix and reservoir-type structures with different porosities were obtained. Scaling up to larger batch sizes resulted in microspheres with a faster drug release. The addition of water-miscible cosolvents to the water-immiscible polymer solution allowed the preparation of microparticles from a drug solution rather than a drug dispersion. Microparticles prepared by the cosolvent method could be separated after shorter time intervals from the aqueous phase; the microspheres had a denser matrix with finely dispersed drug crystals and a slower drug release when compared with microspheres prepared by the dispersion method, which had a more porous structure with larger embedded drug crystals. The cosolvent and dispersion methods present a simple alternative to the w/o/w-solvent evaporation method for the encapsulation of water-soluble drugs with an external water phase.     

Thalamo-cortical interactions modeled by weakly connected oscillators: could the brain use FM radio principles?

Effects of drug content and medium pH on the release of papaverine (PAP) from biodegradable poly(l-lactic acid) [P(L)LA] matrix were investigated to reveal the predominant factors affecting the two-stage diffusion-controlled release mechanism. A drug-dissolved cylindrical matrix (rod; 10 mmx1 mm diameter) was prepared by heat compression method. In the case of a PAP content below 10%, pH was found to have a strong effect on the release rate, and drug content was found to have no effect on the release profile. The release profile consisted of two sequential diffusion stages due to P(L)LA transformation from amorphous to the semicrystalline state prior to release. In the first release stage PAP diffused through the swollen matrix. The release accelerated with increasing medium pH due to an increase in water content in the acidic P(L)LA rod. In the second release stage PAP diffused through the water-filled micropores developed as a result of the polymer crystallization. On the assumption that the drug partition between the polymer and the medium in the micropores affects the diffusion and the partition is controlled by pH, we derived a modified diffusion kinetic equation. The observation that the release decelerated with increasing medium pH can be explained by the derived equation as resulting from the increase in the drug partition to the polymer. In the case where the rods contained more than 15% of PAP, the drug precipitated out as crystals during release. Accordingly, these rods showed a slower release.     

Experimental hypoxemic hypoxia: changes in R2* of brain parenchyma accurately reflect the combined effects of changes in arterial and cerebral venous oxygen saturation

PURPOSE: The objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body. METHODS: The erodible plugs were either prepared by direct compression followed by placing the tablets in the capsule opening or by congealing a meltable plug material directly within the capsule opening. The disintegration/erosion properties of these plugs were determined and optimized for the final delivery system. In order to assure rapid drug release of the capsule content after erosion of the plug, various excipients (fillers, effervescent agents) and drugs with different solubilities were evaluated. The lag time prior to drug release and the subsequent drug release were investigated as function of capsule content, plug composition, plug preparation technique, plug hardness, weight, and thickness. RESULTS: The erosion time of the compressed plugs increased with increasing molecular weight of the hydrophilic polymer (e.g. hydroxypropyl methylcellulose, polyethylene oxide), decreasing filler (lactose) content and decreased with congealable lipidic plugs with increasing HLB-value and inclusion on surfactants. For complete and rapid release of the drug from the capsule body, effervescent agents had to be included in the capsule content. The drug delivery system showed typical pulsatile release profiles with a lag time followed by a rapid release phase. The lag time prior to the pulsatile drug release correlated well with the erosion properties of the plugs and, besides the composition of the plug, could be controlled by the thickness (weight) of the plug. CONCLUSIONS: A single-unit, capsular-shaped pulsatile drug delivery system was developed wherein the pulsatile release was controlled by the erosion properties of a compressed or congealed plug placed within the opening of the capsule opening.     

Polymerization of Acrylonitrile with （Diisopropylamido） Bis（indenyl） Lanthanides

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Drug release from hydrophilic matrices. 1. New scaling laws for predicting polymer and drug release based on the polymer disentanglement concentration and the diffusion layer

Two scaling laws for predicting polymer and drug release profiles from hydrophilic matrices were developed. They were developed on the basis of the diffusion layer and the polymer disentanglement concentration, rho p,dis, the critical polymer concentration below which polymer chains detach off a gelled matrix that is undergoing simultaneous swelling and dissolution. The relation between rho p,dis and molecular weight, M1 for (hydroxypropyl)methylcellulose (HPMC) in water was established as rho p,dis (g/mL) varies M-0.8. This power-law relationship for rho p,dis, along with the diffusion layer adjacent to the gelled matrix, leads to the scaling law of mp(t)/mp(infinity) varies Meq-1.15, where mp(t)/mp(infinity) is the fractional HPMC release. The scaling law explains the observation that polymer and drug release rates decreased sharply with M at low M and approach limiting values at high M. Experimentally, mp(t)/mp(infinity) was found to scale with Meq as mp(t)/mp(infinity) varies Meq-0.93, where Meq is the equivalent matrix molecular weight. Moreover, fractional drug release, md(t)/md(infinity), followed Meq as md(t)/md(infinity) varies Meq-0.48. These two scaling laws imply that, if the release profiles are known for one composition, release profiles for other compositions can be predicted. The above two power laws lead to two master curves for mp(t)/mp(infinity) and md(t)/md(infinity), suggesting that the release mechanism for soluble drugs from HPMC matrices is independent of matrix compositions, presumably via a diffusion-controlled process. Limitations of the power laws are discussed.