Drug release from thermo-responsive self-assembled polymeric micelles composed of cholic acid and poly(N-isopropylacrylamide)

Cholic acid, conjugated with amine-terminated poly(N-isopropylacrylamide) (abbreviated as CA/ATPNIPAAm), was synthesized by a N, N'-dicyclohexyl carbodiimide (DCC)-mediated coupling reaction. Self-assembled CA/ATPNIPAAm micelles were prepared by a diafiltration method in aqueous media. The CA/ATPNIPAAm micelles exhibited a lower critical solution temperature (LCST) at 31.5 degrees C. Micelle sizes measured by photon correlation spectroscopy (PCS) were approximately 31.6+/-5.8 nm. The CA/ATPNIPAAm micelles were spherical and their thermal size transition was observed by transmission electron microscope (TEM). A fluorescence probe technique was used for determining the micelle formation behavior of CA/ATPNIPAAm in aqueous solutions using pyrene as a hydrophobic probe. The critical micelle concentration (CMC) was evaluated as 8.9 x 10(-2) g/L. A drug release study was performed using indomethacin (IN) as a hydrophobic model drug. The release kinetics of IN from the CA/ATPNIPAAm micelles revealed a thermo-sensitivity by the unique character of poly(N-isopropylacrylamide) i.e. the release rate was higher at 25 degrees C than at 37 degrees C.     

盐酸博安霉素注射用温度敏感原位凝胶的研究

本文以泊洛沙姆F127为主要基质材料,复合使用泊洛沙姆F68和高分子材料羟丙基甲基纤维素K4M,制备盐酸博安霉素注射用温度敏感原位凝胶。对凝胶的胶凝温度、流变学、质构特性、电镜结构和体外释放等性能进行了研究,并考察了该制剂在大鼠体内的药代动力学。结果表明,制备的盐酸博安霉素注射用温度敏感原位凝胶在常温下为流动的液体,在人体温度下能够发生相转变,成为具有一定胶凝强度的半固体,方便注射给药,胶凝后呈现三维网状空间结构,药物的扩散和凝胶材料的溶蚀为控制药物释放的主要因素。该制剂具有明显的缓释作用,在大鼠体内可以持续释放48 h以上。     

新型眼用阳离子微乳-原位凝胶的制备及其体外角膜滞留特性的研究

设计了新型眼用阳离子微乳-原位凝胶(cationic microemulsion-in situ gel，CM-ISG)系统，以维生素A棕榈酸酯(vitamin A palmitate，VAP)为模型药物研究了该释药系统的角膜滞留特性，并评价了角膜刺激性。采用外界供能法制备了VAP/CM，考察了维生素A棕榈酸酯阳离子微乳-原位凝胶(vitamin A cationic microemulsion-in situ gel，VAP/CM-ISG)胶凝前后的流变学性质，以及VAP/CM-ISG和市售品诺沛凝胶(Oculotect Gel)中VAP的体外释放和凝胶溶蚀情况；采用束缚泡法研究了VAP/CM-ISG和Oculotect Gel在离体角膜表面的滞留情况，Draize评分法评价了VAP/CM-ISG对兔角膜刺激性。透射电镜表明VAP/CM粒径分布均匀，加入poloxamer 407凝胶材料前后粒径无明显变化；加入VAP/CM后poloxamer 407溶液的胶凝温度下降了1.5 ℃，胶凝后系统的弹性模量增加了15.7倍；VAP/CM-ISG和Oculotect Gel中药物释放和凝胶溶蚀均呈现良好的零级释放特征。解吸附动力学研究发现，VAP/CM-ISG与Oculotect Gel相比，体外角膜滞留时间延长，且角膜接触角减小，具有良好的角膜铺展和滞留效果；兔角膜刺激性评价试验表明，制得的VAP/CM-ISG眼部生理相容性良好。VAP/CM-ISG能综合阳离子微乳和原位凝胶两种剂型的优点，改善药物在角膜表面的铺展性，提高角膜滞留，是一种具有良好应用前景的新型眼用释药系统。     

Nanoparticle layers controlling drug release from emulsions.

The influence of interfacial layers of silica nanoparticles on the release kinetics of a model lipophilic drug (di-butyl-phthalate (DBP)) from polydimethylsiloxane droplets in water is reported. The nanoparticle layers are formed by self-assembly from solution and their structure is controlled by nanoparticle hydrophobicity and the solution conditions. For DBP loading levels resulting in released concentrations below the solubility limit, release is rapid from uncoated droplets whereas significant sustained release is facilitated by rigid interfacial layers of hydrophobic silica nanoparticles. Activation energies for release are in the range 580-630kJmol(-1), which is ten times greater than for barriers introduced by typical polymeric stabilisers. In contrast, at higher DBP loading levels (total concentration greater than the solubility level), both hydrophilic and hydrophobic nanoparticle layers increase the rate and extent of dissolution compared with uncoated droplets and pure DBP solutions. Nanoparticle layers are shown to significantly influence the release kinetics of lipophilic drugs from oil in water emulsions: either sustained or enhanced release properties can be introduced depending on the nanoparticle layer type and drug loading level. Thus, nanoparticle layers may be engineered to facilitate a range of release behaviours and offer great potential in the delivery of poorly soluble drugs.     

Kinetics of degradation and oil solubility of ester prodrugs of a model dipeptide (Gly-Phe)

Oil-based depot formulations may constitute a future delivery method for small peptides. Thus, a requirement is attainment of sufficient oil solubility for such active compounds. A model dipeptide (Gly-Phe) has been converted into lipophilic prodrugs by esterification at the C-terminal carboxylic acid group. The decomposition kinetics of octyl ester of Gly-Phe (IV) has been investigated at pH 7.4 (37 degrees C) and IV was shown to degrade by first-order kinetics via two parallel pathways (1) intramolecular aminolysis resulting in formation of a 2,5-diketopiperazine and (2) hydrolysis of the ester bond producing the dipeptide. The cyclisation reaction was dominating in the decomposition of methyl (II) butyl (III) octyl (IV) decyl (V) and dodecyl (VI) esters of Gly-Phe at pH 7.4. However, this degradation pathway was almost negligible for pH below 6. During degradation of the dipeptide esters in 80% human plasma pH 7.4 (37 degrees C) a minimal amount of cyclo(-Gly-Phe) was formed. A faster degradation of the esters in 80% human plasma pH 7.4 compared to those in aqueous solution pH 7.4 was suggested to be due to fast cleavage of the peptide bond. Low oil solubilities for Gly-Phe and the hydrochlorides of the dipeptide esters III and VI were observed. Although the solubility of Gly-Phe in oil solutions was enhanced by hydrophobic ion pairing with sodium decyl sulfonate the oil solubility was still less than 1 mg Gly-Phe/ml. By addition of a solubiliser, 10% N,N-dimethylacetamide (DMA), to Viscoleo the solubility of the HIP complexes increased significantly. The present study indicates that sufficient oil solubility might only be obtained for relatively small peptides by using the prodrug approach in combination with solubility enhancing organic solvents like DMA.     

可注射更昔洛韦温敏型原位凝胶剂的研究

构建温敏型三嵌段共聚物,研究其理化性质以及用其制备的可注射更昔洛韦温敏型原位凝胶剂的制剂特性。以聚乙二醇（PEG）作为亲水嵌段．丙交酯（LA）和β-丁内酯（β-BL）的无规共聚物PBLA作为疏水嵌段．采用开环聚合法合成温敏型三嵌段共聚物PBLA-PEG-PBLA,并对其理化性质进行表征,考察其溶液的胶凝温度／临界凝胶浓度、流变学性质、通针性和溶蚀行为以及以更昔洛韦作为模型药物、用其制得的可注射载药温敏型原位凝胶剂的体外释放特性。合成的PBLA-PEG-PBLA嵌段共聚物重均分子质量在6000左右,多分散系数为1．5左右;其溶液临界凝胶浓度（g·mL^-1）为5％-10％,质量浓度（g·mL^-1）在10％～25％时胶凝温度为31～35℃,接近并略低于体温：其凝胶在低温下储能模量与黏度较小,当温度接近相转变温度后两者迅速增大：其载药凝胶剂累计释放量经拟合显示遵循一级动力学方程,并呈扩散释药机制。较低质量浓度[10％15％（g·mL^-1）的PBLA—PEG—PBLA更符合玻璃体注射要求,更适用于制备可注射载药温敏型原位凝胶剂。     

Effects of process variables on the encapsulation of oil in ca-alginate capsules using an inverse gelation technique

The objective of this study was to investigate the effects of process variables on the encapsulation of oil in a calcium alginate membrane using an inverse gelation technique. A dispersion of calcium chloride solution in sunflower oil (water-in-oil emulsion) was added dropwise to the alginate solution. The migration of calcium ions to the alginate solution initiates the formation of a ca-alginate membrane around the emulsion droplets. The membrane thickness of wet capsules and the elastic modulus of dry capsules increased following first-order kinetics with an increasing curing time. An increase in the calcium chloride concentration increased the membrane thickness of wet capsules and the elastic modulus of dry capsules. An increase in the alginate concentration decreased the mean diameter of wet capsules but increased the elastic modulus of dry capsules.     

Heat-Treated Emulsions with Cross-Linking Bovine Serum Albumin Interfacial Films and Different Dextran Surfaces: Effect of Paclitaxel Delivery

In this study, a type of biocompatible and biodegradable oil-in-water emulsion for hydrophobic drug delivery was evaluated in vitro and in vivo. Bovine serum albumin (BSA)-dextran conjugates with different dextran molecular weights and different conjugation degrees were used as the emulsifier and stabilizer. Paclitaxel (PTX), a hydrophobic antitumor drug, was effectively loaded inside the oil droplets via high-pressure homogenization. The emulsions were heated at 90° C for 1 h to eliminate the anaphylaxis of BSA. By virtue of the cross-linked BSA films at the oil–water interfaces produced by the heat treatment and the hydrophilic dextran surfaces, the emulsions are stable in blood serum, as well as stable against long-term storage. In vitro cytotoxicity study verifies that the unloaded emulsions are biocompatible and the PTX-loaded emulsions have similar antitumor activity as PTX solution. In vivo investigation of murine ascites hepatoma H22-tumor-bearing mice demonstrates that the PTX-loaded emulsion with shorter and denser dextran surface has better tumor inhibition and survivability efficacy than the commercial PTX injection.     

Smart gelation of chitosan solution in the presence of NaHCO3 for injectable drug delivery system

In situ gelling systems are attractive as injectable vehicles for drug delivery. The present work described a novel gelation process of acidic chitosan solution in the presence of sodium bicarbonate (NaHCO(3)). The NaHCO(3) concentration played an important role in this gelling system. When it came within the appropriate range, the chitosan/NaHCO(3) system would stay at sol state in certain condition and showed sol-gel transition from the top to the bottom after heating. The rheological properties of the gelling system, as well as the morphology and erosion behavior of the formed chitosan hydrogels were evaluated as a function of the NaHCO(3) concentration in sols. The hydrogels showed porous morphologies with some diversification depending on the NaHCO(3) concentration, which also affected their erosion behaviors and drug release rates. Moreover, the gelation mechanism of such chitosan/NaHCO(3) system was studied and proposed as the formation of three-dimensional chitosan network with physical junctions thanks to the deprotonation of -NH(3)(+) in chitosan accompanying with the gradual neutralization between HCO(3)(-) and acid. In vivo gelation test was also performed by the dorsal subcutaneous injection of chitosan/NaHCO(3) solution in rat. The formation of in situ gels suggested such system promising applications in injectable drug delivery system.     

Self-assembled drug delivery system based on low-molecular-weight bis-amide organogelator: synthesis,properties and in vivo evaluation

Context: Orgnaogels based on amino acid derivatives have been widely used in the area of drug delivery.

Objective: An organogel system based on l-lysine derivatives was designed and prepared to induce a thermal sensitive implant with higher transition temperature, better mechanical strength, and shorter gelation time.

Materials and methods: The organogel was prepared by injectable soybean oil and methyl (S)-2,5-ditetradecanamidopentanoate (MDP), which was synthesized for the first time. Candesartan cilexetil (CC) was chosen as model drug. Different formulations were designed and optimized by response surface method. Thermal, rheology properties, and gelation kinetics of the optimized formulation had been characterized. The release behaviors in vitro, as well as in vivo were evaluated in comparison with the oily solution of drugs. Finally, the local inflammation response of in situ organogel was assessed by histological analysis.

Results and discussion: Results showed that the synthesized gelator, MDP, had a good gelation ability and the organogels obtained via the self-assembly of gelators in vegetable oils exhibited great thermal and rheology properties, which guaranteed their state in body. In vivo pharmacokinetic demonstrated that the organogel formulation could extend the drug release and maintain a therapeutically effective plasma concentration at least 10 d. In addition, this implant showed acceptable moderate inflammation.

Conclusion: The in situ forming l-lysine-derivative-based organogel could be a promising matrix for sustained drug delivery of the drugs with low solubility.     

Kinetic study of the transformation of mefenamic acid polymorphs in various solvents and under high humidity conditions

The transformation kinetics of mefenamic acid form II to form I in three kinds of solvents and under high humidity conditions were extensively investigated. Form II crystals were suspended in water, 50% ethanol and ethanol at 28, 33 and 37 degrees C, or stored at 50, 60 and 70 degrees C at 97% RH. Form II transformed to form I under all storage conditions and the rate of transformation depended on the kind of solvent. The transformation followed the three-dimensional nuclei growth mechanism, depending on temperature. The nuclei formation and growth processes were significantly accelerated in ethanol compared with water. The addition of seed crystals of the stable form I shortened the both nuclei formation and growth processes and therefore the transformation was accelerated.     

In vitro and in vivo characterization of scleral implants of indomethacin.

Scleral implants of indomethacin with sodium alginate as carrier were fabricated and evaluated for various physico-chemical properties such as uniformity of thickness, weight, drug content, surface pH, percent dissolution and water up-take capacity (swelling index). The effect of drug particle size, polymer concentration, drug loading, plasticizer concentration, and effects of physical reinforcement (freeze-thawing for 3 and 6 cycles) and chemical cross-linking with calcium chloride, on the in vitro drug release characteristics were evaluated. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis induced (intravitreal injection of Bovine Serum Albumin (BSA)-50 micrograms/ml) rabbit eyes. The release of indomethacin from the prepared implants followed predominantly matrix diffusion kinetics. Swelling and moisture absorption/loss studies correlated well with the in vitro release studies. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells and synechias), in the implanted eye when compared to the control eye in the rabbits.     

Stability of cefazolin sodium in various artificial tear solutions and aqueous vehicles

The stability of cefazolin sodium reconstituted in four artificial tear solutions, two acetate buffer solutions, phosphate buffer solution, and 0.9% sodium chloride injection was studied. Cefazolin was reconstituted in Tearisol, Isopto Tears, Liquifilm Forte, and Liquifilm Tears; acetate buffer solution at pH 4.5 and pH 5.7; phosphate buffer solution at pH 7.5; and 0.9% sodium chloride injection. The solutions were stored at 4 degrees C, 25 degrees C, and 35 degrees C for seven days. All of the solutions were inspected for particulates, turbidity, color, and odor. Five assay determinations on each of three samples of each formulation were performed using a stability-indicating high-performance liquid chromatographic assay. Cefazolin stability was influenced primarily by pH and storage temperature. Reconstitution of cefazolin sodium in the alkaline tear solutions Isopto Tears and Tearisol and in phosphate buffer solution resulted in particulate and color formation at 25 degrees C and 35 degrees C. Turbidity was noted after cefazolin sodium was reconstituted in Isopto Tears. No color or precipitate formation was evident after seven days at 25 degrees C and 35 degrees C in the formulations of acidic pH containing Liquifilm Tears, Liquifilm Forte, 0.9% sodium chloride injection or acetate buffer solution as the vehicles. The extent of degradation of cefazolin was substantially higher in the formulations of alkaline pH than in those of acidic pH at 35 degrees C and 25 degrees C. All of the formulations retained more than 90% of their initial concentration when stored at 4 degrees C. Cefazolin sodium, when reconstituted in artificial tear solutions with an acidic pH, is stable for up to three days at room temperature.     

地塞米松磷酸钠温度敏感原位凝胶的特性研究

本文以泊罗沙姆PluronicF127为温度敏感原位凝胶材料，考察了PluronicF127与PluronicF68不同浓度处方对地塞米松磷酸钠温度敏感原位凝胶的胶凝温度、相转变温度、凝胶强度、稳态黏度、溶蚀和药物释放行为等特性的影响。采用试管倒转法测定胶凝温度；旋转流变仪测定相转变温度、弹性模量、稳态黏度等流变学参数；无膜溶出法测定凝胶的溶蚀行为；HPLC测定地塞米松磷酸钠的释放度。结果表明，随着处方中F127浓度的增高，凝胶的胶凝温度和相转变温度降低，黏度和弹性模量增加，溶蚀速率和药物释放速率减慢；而处方中F68对凝胶特性的影响与F127相反。温度敏感原位凝胶在低温时为牛顿流体，黏度很小；随着温度升高，黏度增大；当增至相转变温度附近，表现出典型的假塑性流体特征；药物释放速率受控于凝胶溶蚀速率，二者遵循零级动力学方程。处方中含F127 22.5% / F68 2.5%的地塞米松磷酸钠温度敏感原位凝胶的性质与临床治疗要求基本吻合，有望在临床中获得应用。     

Encapsulation of submicrometer-sized 2-methoxyestradiol crystals into polymer multilayer capsules for biological applications

A facile approach has been developed to encapsulate submicrometer-sized drug crystals into polymer multilayer capsules produced by sequential deposition of polymers onto the drug particle surfaces. 2-Methoxyestradiol (2-ME) is a hydrophobic metabolite of 17-beta estradiol, which has been demonstrated as a potential anticancer agent. It was selected as a model drug and was formulated into submicrometer-sized particles through fine milling followed by intense sonication in the presence of dipalmitoyl-dl-(R)-phosphatidylcholine (DPPC). The reserved positive charges on the 2-ME crystal surface by DPPC enhanced the water solubility of the particles and subsequent self-assembly of dextran sulfate (DS) and dextran (DN) multilayers through hydrogen bonding and physical adsorption. Upon the exposure of the drug capsules to ethanol, hollow DS/DN multilayer polymer shells can be formed. The encapsulation process and hollow polymer multilayer shell formation were confirmed by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM), while the surface morphology of the formed drug capsules was investigated using scanning electron microscopy (SEM). In vitro studies show that the inhibitory effect of the formed 2-ME capsules is the same as that of the conventional formulation of 2-ME in a concentrated ethanol solution, as demonstrated by dramatic changes in cell morphology and significantly decreased viability of target cells. We also demonstrate that the change of the outermost layer of the drug capsules does not significantly influence its bioactivity. The presented strategy to encapsulate submicrometer-sized hydrophobic drug particles is expected to provide a general pathway to fabricate drug capsules for various biological applications.     

Preparation and evaluation of microcapsules using polymerized rosin as a novel wall forming material

Sustained release diclofenac sodium microcapsules were prepared using polymerized rosin as a novel wall-forming material by a solvent evaporation technique. A novel method developed in our laboratory with the potential for scale-up and production of polymerized rosin microcapsules is detailed. These microcapsules might have application for development of implant/depot systems, primarily due to a sustained/controlled release capability and potential biocompatibility of polymerized rosin. The effect of variables like solvent systems, stirring speed and temperature were previously optimized. The solution system of drug and polymerized rosin dissolved in iso-propyl alcohol and acetone is sprayed with the help of a 0.5 mm nozzle spray gun in liquid paraffin maintained at 60 degrees C in the stirring condition. Varying drug:polymer ratios, namely 1:1, 1:2, 2:1, 1:3 and 3:1, were employed for microcapsule preparation. The prepared microcapsules were evaluated for size, shape, drug content and in vitro drug release. The morphology of microcapsules was characterized by scanning electron microscopy. The microcapsules show sustained release curves at pH 7.4 phosphate buffer for up to 10 h. The data obtained from the dissolution profiles were compared in the light of different kinetics models and the regression coefficients were compared. The in vitro dissolution study confirmed the Higuchi-order release pattern. Particle size and release data analysis from five consecutive batches prepared in the laboratory indicated suitable reproducibility of the proposed solvent evaporation process.     

Isothermal microcalorimetry and inverse phase gas chromatography to study small changes in powder surface properties

To investigate the effects of additives on the physicochemical properties of in situ gelling and mucoadhesive liquid suppository base, gelation temperature, gel strength and bioadhesive force of liquid suppository base, poloxamer 407 (P 407) and poloxamer 188 (P 188) (15/15%) were evaluated in the presence of following additives: solvent (ethanol, propylene glycol, glycerin), ionic strength-controlling agent (sodium chloride) and pH-controlling agent (hydrochloric acid, sodium monohydrogen phosphate, sodium dihydrogen phosphate). Among the additives studied, sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate increased to a great extent the gel strength and the bioadhesive force of P 407/P 188 (15/15%) with a decrease in gelation temperature. Glycerin slightly decreased the gelation temperature and slightly increased the gel strength and bioadhesive force. However, the addition of 1% of sodium chloride, sodium monohydrogen phosphate or sodium dihydrogen phosphate caused a greater than 60-fold increase in gel strength and over a tenfold increase in bioadhesive force with 2-4 degrees C decrease of gelation temperature within optimal range, compared with P 407/P 188 (15/15%) alone. On the other hand, ethanol, propylene glycol and hydrochloric acid increased the gelation temperature and slightly decreased the gel strength and the bioadhesive force. Taken together, these findings indicate that the effect of additives on the physicochemical properties of liquid suppository bases depends on their bonding capacities, in that additives such as sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate having strong cross-linking bonds with the components of liquid suppository base increase the strength and bioadhesive force of a gel compared to liquid suppository base alone, while additives such as ethanol, propylene glycol and hydrochloric acid having weaker hydrogen bonding result in a weaker response. Thus, sodium chloride and sodium phosphates appear to be promising additives for in situ gelling and mucoadhesive liquid suppository base, if used in adequate amounts.     

The relationship between structures and in vitro properties of a polyanhydride implant containing gentamicin sulfate.

Laboratory scale injection-molding equipment was utilized to fabricate an implant consisting of poly(FAD:SA 1:1) and 20% (w/w) gentamicin sulfate. Characterizations were performed to determine the molecular weight and glass transition temperature of poly(FAD:SA 1:1). A study was carried out to investigate the relationships between the in vitro performance, morphology, and micro-structures of the molded implants. It was found that implants produced with different structures exhibited different physical integrities in water, i.e., cracking or non-cracking. For the non-cracking implants, a skin-core structure formed by an oriented skin layer was observed under a polarized light microscope. The same morphology was not seen in the cracking implants. The crystal orientation in the skin layer of the non-cracking implants was further identified using a wide-angle x-ray diffraction method (WAXD). No crystal orientation could be found in the cracking implants by WAXD. Furthermore, studies were carried out to evaluate the in vitro drug release for implants showing different degrees of integrity in water. The in vitro drug release of the cracking implants was markedly faster than that of the non-cracking implants due to the pronounced initial drug-burst effect as a result of crack formation in the implants.     

Release characteristics of salmon calcitonin from dextran hydrogels for colon-specific delivery.

Biodegradable dextran hydrogels were synthesized by crosslinking dextran (T-70) with epichlorohydrin (ECH) for the in vitro colon-specific delivery of salmon calcitonin (sCT). Crosslinking reaction was performed in 2.8 M NaOH solution both in the presence and absence of ethanol at 10 and 23 degrees C. Biodegradation kinetics of dextran hydrogels were studied and, in the presence of 0.7 IU ml-1 dextranase, dextran discs lost 71.0% and 56.5% of their dry weight within 80 h at pH 5.5 and 7.0, respectively. sCT was derivatized with the fluorescamine (FSM) at borate buffer (pH 9.0) and the quantitative determinations were performed using spectrofluorimetric method (lambdaex: 390 nm, lambdaem: 475 nm). In vitro release studies for the hydrogels prepared in the presence of ethanol were carried out in simulated gastrointestinal fluids. Results indicated that 84.9% of the loaded-sCT was released for 17 h and dextran hydrogel prepared in the presence of ethanol may be a good delivery device for the colon-specific delivery of other peptide-type drugs as well as sCT.     

The Relationship Between Structures and In Vitro Properties of a Polyanhydride Implant Containing Gentamicin Sulfate

Laboratory scale injection-molding equipment was utilized to fabricate an implant consisting of poly(FAD:SA 1:1) and 20% (w/w) gentamicin sulfate. Characterizations were performed to determine the molecular weight and glass transition temperature of poly(FAD:SA 1:1). A study was carried out to investigate the relationships between the in vitro performance, morphology, and micro-structures of the molded implants. It was found that implants produced with different structures exhibited different physical integrities in water, i.e., cracking or non-cracking. For the non-cracking implants, a skin–core structure formed by an oriented skin layer was observed under a polarized light microscope. The same morphology was not seen in the cracking implants. The crystal orientation in the skin layer of the non-cracking implants was further identified using a wide-angle x-ray diffraction method (WAXD). No crystal orientation could be found in the cracking implants by WAXD. Furthermore, studies were carried out to evaluate the in vitro drug release for implants showing different degrees of integrity in water. The in vitro drug release of the cracking implants was markedly faster than that of the non-cracking implants due to the pronounced initial drug-burst effect as a result of crack formation in the implants.